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Bordetella pertussis infection is a highly contagious respiratory disease that can cause complications such as pneumonia and death. A total of 62,646 cases of pertussis worldwide were reported by WHO in 2022. This study aimed to obtain the pertussis seroprevalence and sociodemographic data in children aged 1–14 years and its association factors in the community based on Riskesdas 2013 and 2018. Bivariate and multivariate analysis was carried out on data from 12,753 children aged 1–14 years collected from Riskesdas 2013 and 2018 in Indonesia. Pertussis serology data was obtained based on the results of the ELISA examination which was categorized as seropositive if anti-pertussis toxin IgG ≥ 100 IU/mL or anti-pertussis IgG > 11 NTU. Pertussis seropositive indicated recent pertussis infection if no pertussis vaccine was received within the last twelve months. Pertussis seroprevalence was found at 9.8% and 33.4% in Riskesdas 2013 and 2018 respectively. While 10.1% of children aged 5–14 years were found pertussis seropositive by excluding the possible effect of vaccination in the last twelve months in Riskesdas 2013. The most important associated factor in seropositive pertussis at ages 1–4 years and 5–14 years was a history of pneumonia in the last month (OR = 2.709, 95%CI: 2.592–2.831 in Riskesdas 2013 and OR = 2.421, 95%CI: 2.299–2.550 in Riskesdas 2018). In the adjusted analysis for respondents' characteristics, low maternal education was the predictive factor that most influenced pertussis seropositivity, especially in the 2013 Riskesdas (APOR = 2.983, 95%CI: 2.670–3.333). In conclusion, the results of this study showed that the seroprevalence of pertussis was high, especially in children aged 5–14 years, so that pertussis vaccine booster administration could be considered. Because the most influencing factor towards pertussis seropositive was low maternal education, the groups of children with low-educated mothers should be targets for strengthening complete vaccination coverage and disease control. [ABSTRACT FROM AUTHOR]

Background: Decision-makers in middle-income countries need evidence on the cost-effectiveness of COVID-19 booster doses and oral antivirals to appropriately prioritise these healthcare interventions. Methods: We used a dynamic transmission model to assess the cost-effectiveness of COVID-19 booster doses and oral antivirals in Fiji, Indonesia, Papua New Guinea, and Timor-Leste. We conducted cost-effectiveness analysis from both healthcare and societal perspectives using data collated from publicly available sources. We developed an interactive R Shiny which allows the user to vary key model assumptions, such as the choice of discounting rate, and view how these assumptions affect model results. Findings: Booster doses were cost saving and therefore cost-effective in all four middle-income settings from both healthcare and societal perspectives using 3% discounting. Providing oral antivirals was cost-effective from a healthcare perspective if procured at a low generic price (US$25) or middle-income reference price (US$250); however, their cost-effectiveness was strongly influenced by rates of wastage or misuse, and the ongoing costs of care for patients hospitalised with COVID-19. The cost or wastage of rapid antigen tests did not appear strongly influential over the cost-effectiveness of oral antivirals in any of the four study settings. Conclusions: Our results support that COVID-19 booster programs are cost-effective in middle-income settings. Oral antivirals demonstrate the potential to be cost-effective if procured at or below a middle-income reference price of US$250 per schedule. Further research should quantify the rates of wastage or misuse of oral COVID-19 antivirals in middle-income settings. [ABSTRACT FROM AUTHOR]

Background: Pacific Islanders are underrepresented in vaccine efficacy trials. Few studies describe their immune response to COVID-19 vaccination. Yet, this characterization is crucial to re-enforce vaccination strategies adapted to Pacific Islanders singularities. Methods and findings: We evaluated the humoral immune response of 585 adults, self-declaring as Melanesians, Europeans, Polynesians, or belonging to other communities, to the Pfizer BNT162b2 vaccine. Anti-spike and anti-nucleoprotein IgG levels, and their capacity to neutralize SARS-CoV-2 variants and to mediate antibody-dependent cellular cytotoxicity (ADCC) were assessed across communities at 1 and 3 months post-second dose or 1 and 6 months post-third dose. All sera tested contained anti-spike antibodies and 61.3% contained anti-nucleoprotein antibodies, evidencing mostly a hybrid immunity resulting from vaccination and SARS-CoV-2 infection. At 1-month postimmunization, the 4 ethnic communities exhibited no significant differences in their anti-spike IgG levels (p value = 0.17, in an univariate linear regression model), in their capacity to mediate omicron neutralization (p value = 0.59 and 0.60, in an univariate logistic regression model at 1-month after the second and third dose, respectively) and in their capacity to mediate ADCC (p value = 0.069 in a multivariate linear regression model), regardless of the infection status. Anti-spike IgG levels and functionalities of the hybrid humoral immune response remained equivalent across the 4 ethnic communities during follow-up and at 6 months post-third dose. Conclusions: Our study evidenced Pacific Islander's robust humoral immune response to Pfizer BNT162b2 vaccine, which is pivotal to re-enforce vaccination deployment in a population at risk for severe COVID-19 (clinicaltrials.gov: NCT05135585). Trial registration: This trial has been register in ClinicalTrials.gov (ID: NCT05135585). Catherine Camille Inizan and colleagues evaluate the hybrid humoral immune response to COVID-19 infection and vaccination across a variety of Pacific Islander communities, and present data on a poorly studied population. Author summary: Why was this study done?: Pacific Islanders are at risk for severe COVID-19, in part owing to lifestyle and high rate of comorbidities. In a few studies, ethnicity had no impact on antibody levels following Pfizer BNT162b2 vaccine in Pacific Islanders; in these studies, however, follow-up was reduced and no distinction was made between the different Pacific ethnic communities. Characterizing the levels and functionality of Pacific Islanders humoral immune response to Pfizer BNT162b2 vaccine is pivotal to adapt vaccination regimens to regional singularities. What did the researchers do and find?: The current study enrolled 585 participants from New Caledonia self-declaring as Melanesians, Polynesians, Europeans, or belonging to other communities. Antibody levels and their functionality were characterized at the following time points: (1) 1 and/or 3 months after a second dose of the Pfizer BNT162b2 vaccine was administered; or (2) 1 and/or 6 months after the third dose of the vaccine. Approximately 61.3% of all sera contained traces of previous SARS-CoV-2 infection; the cohort's immune response was thus mostly hybrid, resulting from both vaccination and infection. At all time points analyzed, the hybrid humoral immune response remained equivalent across the Melanesian, Polynesian, European, and other communities: anti-spike antibody levels, which mirror the strength of the immune response, but also the capacity to mediate omicron neutralization and the capacity to mediate antibody-dependent cellular cytotoxicity (ADCC) were not significantly different across communities (p values >0.05). What do these findings mean?: The lack of community effect, despite different prevalence of obesity, suggests that SARS-CoV-2 hybrid humoral response does not differ between communities. Such robust and prototypical humoral immune response to Pfizer BNT162b2 vaccine and SARS-CoV-2 in Pacific Islanders is of prime importance to foster booster doses roll-out, with the aim to better protect this understudied population which is vulnerable to severe COVID-19. Biological confirmation of ethnicity and a larger sample size in the Polynesian community would enhance the resolution of our findings. [ABSTRACT FROM AUTHOR]

The COVID-19 booster immunization policy is cost-effective, but evidence on additional booster doses and appropriate strategies is scarce. This research compared the cost-effectiveness of annual, twice-a-year, and biennial booster dose policies. We performed stochastic modeling using compartmental susceptible-exposed-infectious-recovered models and a system dynamic model. We evaluated four policy scenarios: (1) hypothetical no-booster immunization policy; (2) twice-a-year vaccination policy; (3) annual vaccination policy; and (4) biennial vaccination policy. In addition, we conducted a one-way sensitivity analysis by adjusting R0 from 1.8 to 3.0 in all scenarios (epidemic stage) and by decreasing the vaccination cost by 50% at the end of the first year to reflect the current policy direction to enhance domestic vaccine production. Compared to non-booster policies, all three booster strategies reduced the number of cases, hospital admissions, and severe infections remarkably. Without a booster, total cases would reach 16,220,615 (95% confidence interval [CI] 6,726,550–29,661,112) by day 1,460, whereas, with a twice-a-year booster, the total cases would reach 597,901 (95% CI 526,230–694,458) in the same period. Even though the no booster scenario exhibited the lowest cost by approximately the first 500 days, by day 1,460 the biennial booster scenario demonstrated the lowest cost at 72.0 billion baht (95% CI 68.6–79.4 billion). The most cost-saving policy was the biennial booster scenario. The annual booster scenario also stood as a cost-effective option for most outcomes. In the epidemic stage and in an assumption where the vaccination costs dropped, all booster policies became more cost-effective or cost-saving compared with the main assumption. This study underscores the significance of the COVID-19 vaccine booster policy. Implementing policies should take into consideration cost-effectiveness, feasibility, and public communication. [ABSTRACT FROM AUTHOR]

Live-attenuated influenza vaccines (LAIV) offer advantages over the commonly used inactivated split influenza vaccines. However, finding the optimal balance between sufficient attenuation and immunogenicity has remained a challenge. We recently developed an alternative LAIV based on the 2009 pandemic H1N1 virus with a truncated NS1 protein and lacking PA-X protein expression (NS1(1–126)-ΔPAX). This virus showed a blunted replication and elicited a strong innate immune response. In the present study, we evaluated the efficacy of this vaccine candidate in the porcine animal model as a pertinent in vivo system. Immunization of pigs via the nasal route with the novel NS1(1–126)-ΔPAX LAIV did not cause disease and elicited a strong mucosal immune response that completely blocked replication of the homologous challenge virus in the respiratory tract. However, we observed prolonged shedding of our vaccine candidate from the upper respiratory tract. To improve LAIV safety, we developed a novel prime/boost vaccination strategy combining primary intramuscular immunization with a haemagglutinin-encoding propagation-defective vesicular stomatitis virus (VSV) replicon, followed by a secondary immunization with the NS1(1–126)-ΔPAX LAIV via the nasal route. This two-step immunization procedure significantly reduced LAIV shedding, increased the production of specific serum IgG, neutralizing antibodies, and Th1 memory cells, and resulted in sterilizing immunity against homologous virus challenge. In conclusion, our novel intramuscular prime/intranasal boost regimen interferes with virus shedding and transmission, a feature that will help combat influenza epidemics and pandemics. Author summary: Nasally administered live-attenuated influenza vaccines induce a mucosal immune response that can effectively prevent primary infection and virus shedding. However, the development of alternative live vaccine strategies must consider the balance between eliciting a robust immune response and reducing the virulence of the vaccine candidate. To address this problem, we have developed a novel prime/boost vaccination strategy consisting of an initial intramuscular immunization with a propagation-defective RNA virus vector and subsequent nasal immunization with a modified attenuated influenza virus that has lost its ability to counteract the host innate immune response. Using the porcine model, we demonstrate that this novel strategy is capable of eliciting a robust immune response both systemically and at mucosal surfaces. Importantly, intranasal infection with homologous challenge virus remained undetectable in vaccinated animals. In conclusion, our innovative vaccination regimen represents a promising strategy to control influenza disease and virus spread in both humans and livestock. [ABSTRACT FROM AUTHOR]

Introduction: The impact of SARS-CoV-2 infection among people living with HIV (PLWH) has been a matter of research. We evaluated the incidence and factors associated with SARS-CoV-2 diagnosis among PLWH. We also assessed factors related to vaccination coverage in the Balearic Islands. Methods: A retrospective analytical study was performed, including patients from the Balearic cohort (EVHIA) who were visited at least twice between 1st January 2020 and 31st March 2022. Chi-square test and Mann-Whitney U test were used to compare categorical and continuous variables respectively. Multivariable Cox proportional hazards regression models were estimated to identify risk factors. Results: A total of 3567 patients with HIV were included. The median age was 51 years (IQR 44–59). Most of them were male (77,3%), from Europe (82,1%) or South America (13,8%). During the study period 1036 patients were diagnosed with SARS-CoV-2 infection (29%). The incidence rate was 153,24 cases per 1000 person-year. After multivariable analysis, men who have sex with men (MSM) were associated with an increased risk of SARS-CoV-2 infection (adjusted hazard ratio 1,324, 95% CI 1,138–1,540), whereas African origin, tobacco use and complete or booster vaccination coverage were negatively related. Overall, complete vaccination or booster coverage was recorded in 2845 (79,75%) patients. When analysing vaccination uptake, older patients (adjusted hazard ratio 5,122, 95% CI 3,170–8,288) and those with a modified comorbidity index of 2–3 points (adjusted hazard ratio 1,492, 95% CI 1,056–2,107) had received more vaccine doses. Conclusions: In our study no HIV related factor was associated with an increased risk of SARS-CoV-2 infection, except for differences in the transmission route. Possible confounding variables such as mask wearing or social interactions could not be measured. Vaccines were of utmost importance to prevent SARS-CoV-2 infection. Efforts should be made to encourage vaccination in those groups of PLWH with less coverage. [ABSTRACT FROM AUTHOR]

The rapid development of vaccines against SARS-CoV-2 altered the course of the COVID-19 pandemic. In most countries, vaccinations were initially targeted at high-risk populations, including older individuals and healthcare workers. Now, despite substantial infection- and vaccine-induced immunity in host populations worldwide, waning immunity and the emergence of novel variants continue to cause significant waves of infection and disease. Policy makers must determine how to deploy booster vaccinations, particularly when constraints in vaccine supply, delivery and cost mean that booster vaccines cannot be administered to everyone. A key question is therefore whether older individuals should again be prioritised for vaccination, or whether alternative strategies (e.g. offering booster vaccines to the individuals who have most contacts with others and therefore drive infection) can instead offer indirect protection to older individuals. Here, we use mathematical modelling to address this question, considering SARS-CoV-2 transmission in a range of countries with different socio-economic backgrounds. We show that the population structures of different countries can have a pronounced effect on the impact of booster vaccination, even when identical booster vaccination targeting strategies are adopted. However, under the assumed transmission model, prioritising older individuals for booster vaccination consistently leads to the most favourable public health outcomes in every setting considered. This remains true for a range of assumptions about booster vaccine supply and timing, and for different assumed policy objectives of booster vaccination. Author summary: Computational modelling is used increasingly to assess interventions against infectious diseases. For COVID-19, booster vaccines are being deployed worldwide to mitigate the effect of waning immunity following past infections and vaccinations, and to protect against new SARS-CoV-2 variants. However, booster vaccine availability is limited, making it necessary to consider who should receive booster vaccinations. It is essential that booster vaccine prioritisation is considered not only in the context of high income countries, but also low and middle income countries where the population age structure is very different. We have therefore developed a computational model to guide booster vaccination prioritisation in different socio-economic settings. We show that vaccinated populations can have different compositions between countries, even when identical booster vaccination strategies are adopted. Despite these differences, our modelling results suggest that booster vaccination strategies prioritising the oldest individuals lead to the best possible public health outcomes, due to the substantial skew in the risk of severe outcomes of infection towards older (and other vulnerable) hosts. This remains true even when quantifying the extent of premature, rather than absolute, mortality. This research therefore supports policy advice recommending prioritisation of older individuals for booster vaccines in countries worldwide when vaccine supply is limited. [ABSTRACT FROM AUTHOR]

Hantaviruses are single-stranded RNA viruses belonging to the family Bunyaviridae that causes hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS) worldwide. Currently, there is no effective vaccination or therapy available for the treatment of hantavirus, hence there is a dire need for research to formulate therapeutics for the disease. Computational vaccine designing is currently a highly accurate, time and cost-effective approach for designing effective vaccines against different diseases. In the current study, we shortlisted highly antigenic proteins i.e., envelope, and nucleoprotein from the proteome of hantavirus and subjected to the selection of highly antigenic epitopes to design of next-generation multi-epitope vaccine constructs. A highly antigenic and stable adjuvant was attached to the immune epitopes (T-cell, B-cell, and HTL) to design Env-Vac, NP-Vac, and Com-Vac constructs, which exhibit stronger antigenic, non-allergenic, and favorable physiochemical properties. Moreover, the 3D structures were predicted and docking analysis revealed robust interactions with the human Toll-like receptor 3 (TLR3) to initiate the immune cascade. The total free energy calculated for Env-Vac, NP-Vac, and Com-Vac was -50.02 kcal/mol, -24.13 kcal/mol, and -62.30 kcal/mol, respectively. In silico cloning, results demonstrated a CAI value for the Env-Vac, NP-Vac, and Com-Vac of 0.957, 0.954, and 0.956, respectively, while their corresponding GC contents were 65.1%, 64.0%, and 63.6%. In addition, the immune simulation results from three doses of shots released significant levels of IgG, IgM, interleukins, and cytokines, as well as antigen clearance over time, after receiving the vaccine and two booster doses. Our vaccines against Hantavirus were found to be highly immunogenic, inducing a robust immune response that demands experimental validation for clinical usage. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to map the existing literature to identify predictors of COVID-19 vaccine acceptability among refugees, immigrants, and other migrant populations. Methods: A systematic search of Medline, Embase, Scopus, APA PsycInfo and Cumulative Index of Nursing and Allied Health Literature (CINAHL) was conducted up to 31 January 2023 to identify the relevant English peer-reviewed observational studies. Two independent reviewers screened abstracts, selected studies, and extracted data. Results: We identified 34 cross-sectional studies, primarily conducted in high income countries (76%). Lower vaccine acceptance was associated with mistrust in the host countries' government and healthcare system, concerns about the safety and effectiveness of COVID-19 vaccines, limited knowledge of COVID-19 infection and vaccines, lower COVID-19 risk perception, and lower integration level in the host country. Female gender, younger age, lower education level, and being single were associated with lower vaccine acceptance in most studies. Additionally, sources of information about COVID-19 and vaccines and previous history of COVID-19 infection, also influence vaccine acceptance. Vaccine acceptability towards COVID-19 booster doses and various vaccine brands were not adequately studied. Conclusions: Vaccine hesitancy and a lack of trust in COVID-19 vaccines have become significant public health concerns within migrant populations. These findings may help in providing information for current and future vaccine outreach strategies among migrant populations. [ABSTRACT FROM AUTHOR]

Antibody-mediated immunity plays a key role in protection against SARS-CoV-2. We characterized B-cell-derived anti-SARS-CoV-2 RBD antibody repertoires from vaccinated and infected individuals and elucidate the mechanism of action of broadly neutralizing antibodies and dissect antibodies at the epitope level. The breadth and clonality of anti-RBD B cell response varies among individuals. The majority of neutralizing antibody clones lose or exhibit reduced activities against Beta, Delta, and Omicron variants. Nevertheless, a portion of anti-RBD antibody clones that develops after a primary series or booster dose of COVID-19 vaccination exhibit broad neutralization against emerging Omicron BA.2, BA.4, BA.5, BQ.1.1, XBB.1.5 and XBB.1.16 variants. These broadly neutralizing antibodies share genetic features including a conserved usage of the IGHV3-53 and 3–9 genes and recognize three clustered epitopes of the RBD, including epitopes that partially overlap the classically defined set identified early in the pandemic. The Fab-RBD crystal and Fab-Spike complex structures corroborate the epitope grouping of antibodies and reveal the detailed binding mode of broadly neutralizing antibodies. Structure-guided mutagenesis improves binding and neutralization potency of antibody with Omicron variants via a single amino-substitution. Together, these results provide an immunological basis for partial protection against severe COVID-19 by the ancestral strain-based vaccine and indicate guidance for next generation monoclonal antibody development and vaccine design. Author summary: Antibody-mediated immunity serves as a key element of protection against SARS-CoV-2. B-cell-derived anti-SARS-CoV-2 RBD antibody repertoires from vaccinated and infected individuals were characterized and genetic and molecular features of antibody breadth and potency against viruses were elucidated. A portion of anti-RBD antibody clones that develops after a primary series or booster dose of ancestral strain-based COVID-19 vaccination exhibit broad neutralization against Omicron variants. For example, antibody JL-8C recognizes a distinct epitope (Class 3b epitope) below the tip of RBD opposite to the epitope targeted by FD-11A or S309, and potently neutralizes Omicron variants BA.4/5, XBB.1.5 and XBB.1.16. Our findings suggest that with repeated antigen exposures the antibody repertoire had broadened with epitopes partially overlapping the classically defined set identified early in the pandemic. [ABSTRACT FROM AUTHOR]

Background: In Australian remote communities, First Nations children with otitis media (OM)-related hearing loss are disproportionately at risk of developmental delay and poor school performance, compared to those with normal hearing. Our objective was to compare OM-related hearing loss in children randomised to one of 2 pneumococcal conjugate vaccine (PCV) formulations. Methods and findings: In 2 sequential parallel, open-label, randomised controlled trials (the PREVIX trials), eligible infants were first allocated 1:1:1 at age 28 to 38 days to standard or mixed PCV schedules, then at age 12 months to PCV13 (13-valent pneumococcal conjugate vaccine, +P) or PHiD-CV10 (10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine, +S) (1:1). Here, we report prevalence and level of hearing loss outcomes in the +P and +S groups at 6-monthly scheduled assessments from age 12 to 36 months. From March 2013 to September 2018, 261 infants were enrolled and 461 hearing assessments were performed. Prevalence of hearing loss was 78% (25/32) in the +P group and 71% (20/28) in the +S group at baseline, declining to 52% (28/54) in the +P groups and 56% (33/59) in the +S group at age 36 months. At primary endpoint age 18 months, prevalence of moderate (disabling) hearing loss was 21% (9/42) in the +P group and 41% (20/49) in the +S group (difference −19%; (95% confidence interval (CI) [−38, −1], p = 0.07) and prevalence of no hearing loss was 36% (15/42) in the +P group and 16% (8/49) in the +S group (difference 19%; (95% CI [2, 37], p = 0.05). At subsequent time points, prevalence of moderate hearing loss remained lower in the +P group: differences −3%; (95% CI [−23, 18], p = 1.00 at age 24 months), −12%; (95% CI [−30, 6], p = 0.29 at age 30 months), and −9%; (95% CI [−23, 5], p = 0.25 at age 36 months). A major limitation was the small sample size, hence low power to reach statistical significance, thereby reducing confidence in the effect size. Conclusions: In this study, we observed a high prevalence and persistence of moderate (disabling) hearing loss throughout early childhood. We found a lower prevalence of moderate hearing loss and correspondingly higher prevalence of no hearing loss in the +P group, which may have substantial benefits for high-risk children, their families, and society, but warrant further investigation. Trial registration: ClinicalTrials.gov NCT01735084 and NCT01174849 Amanda Leach and colleagues compare two pneumococcal conjugate vaccines to examine the impact on hearing loss Author summary: Why was this study done?: Chronic otitis media (OM) (middle ear infection) causes hearing loss, which is linked to developmental delay, poor school readiness, attendance, and performance. Almost every Australian First Nations child living in remote regions experiences chronic OM throughout their formative early years. Vaccines effective against OM pathogens, namely, pneumococcus and nontypeable Haemophilus influenzae, could reduce chronic early childhood hearing loss and change the trajectory of disadvantage. Two pneumococcal conjugate vaccines with different formulations potentially protect from infection by either 13 pneumococcal strains (PCV13), or 10 of these 13 pneumococcal strains plus all nontypeable H. influenzae (PHiD-CV10). Our hypothesis was that PHiD-CV10 would be superior to PCV13 in preventing hearing loss. No study had compared PCV13 and PHiD-CV10 in head-to-head or combination schedules. What did the researchers do and find?: We designed 2 consecutive (primary course then booster dose) randomised controlled trials of head-to-head and combination PCV13 and PHiD-CV10 schedules. Audiologists assessed hearing at 6-monthly visits from age 12 to 36 months. Moderate (disabling) hearing loss was detected in 42% (25/60), 32% (29/91), 34% (29/86), 33% (37/111), and 19% (22/113) children at ages 12, 18, 24, 30, and 36 months, respectively. Hearing Australia's recommendation for hearing assistance was met in around 70% children at ages 12 (67%, 40/60), 18 (69%, 63/91), and 24 months (71%, 61/86), respectively. Contrary to our hypothesis, PHiD-CV10 vaccine was not superior to PCV13 in reducing hearing loss. At primary endpoint age 18 months, the prevalence of moderate (disabling) hearing loss was halved in the PCV13 group (21% (9/42) compared to 41% (20/49) in the PHiD-CV10 group, and the prevalence of no hearing loss was double (36% and 16%, respectively). At ages 24, 30, and 36 months, this trend continued but differences were smaller. What do these findings mean?: The 19% lower prevalence of moderate hearing loss and 19% higher prevalence of no hearing loss in the PCV13 group at age 18 months is potentially highly clinically significant, particularly as the trend appears to be sustained, albeit smaller. Our study emphasises the importance of innovative and targeted research designs that meet the needs of high-risk populations and are independent of the pharmaceutical industry. Pneumococcal conjugate vaccine trials should evaluate impacts on child development. The small sample size creates uncertainty about the plausible difference in hearing between the two vaccines. We are 95% confident that the true difference is between 1% and 37%. [ABSTRACT FROM AUTHOR]

Background: Persons who inject drugs (PWID) may be unengaged with healthcare services and face an elevated risk of severe morbidity and mortality associated with COVID-19 due to chronic diseases and structural inequities. However, data on COVID-19 vaccine uptake, particularly booster vaccination, among PWID are limited. We examined COVID-19 vaccine uptake and factors associated with booster vaccination among PWID in New York City (NYC). Methods: We recruited PWID using respondent-driven sampling from October 2021 to November 2023 in a survey that included HIV and SARS-CoV-2 antibodies testing. The questionnaire included demographics, COVID-19 vaccination and attitudes, and drug use behaviors. Results: Of 436 PWID, 80% received at least one COVID-19 vaccine dose. Among individuals who received at least one COVID-19 vaccine dose, 95% were fully vaccinated. After excluding participants recruited before booster authorization for general adults started in NYC, and those who had never received an initial vaccination, 41% reported having received a COVID-19 booster vaccine dose. COVID-19 booster vaccination was significantly associated with having a high school diploma or GED (adjusted odds ratio (aOR) 1.93; 95% confidence interval (CI) 1.09, 3.48), ever received the hepatitis A/B vaccine (aOR 2.23; 95% CI 1.27, 3.96), main drug use other than heroin/speedball, fentanyl and stimulants (aOR 14.4; 95% CI 2.32, 280), number of non-fatal overdoses (aOR 0.35; 95% CI 0.16, 0.70), and mean vaccination attitude score (aOR 0.94; 95% CI 0.89, 0.98). Conclusions: We found a suboptimal level of COVID-19 booster vaccination among PWID, which was consistent with the rates observed in the general population in NYC and the U.S. Community-based interventions are needed to improve COVID-19 booster vaccination access and uptake among PWID. Attitudes towards vaccination were significant predictors of both primary and booster vaccination uptake. Outreach efforts focusing on improving attitudes towards vaccination and educational programs are essential for reducing hesitancy and increasing booster vaccination uptake among PWID. [ABSTRACT FROM AUTHOR]

Background: Yellow fever (YF), a mosquito-borne viral hemorrhagic fever, is endemic in Uganda and causes frequent outbreaks. A total of 1.6 million people were vaccinated during emergency mass immunization campaigns in 2011 and 2016. This study explored local perceptions of YF emergency mass immunization among vulnerable groups to inform future vaccination campaigns. Methodology: In this qualitative study, we conducted 43 semi-structured interviews, 4 focus group discussions, and 10 expert interviews with 76 participants. Data were collected in six affected districts with emergency mass vaccination. We included vulnerable groups (people ≥ 65 years and pregnant women) who are typically excluded from YF vaccination except during mass immunization. Data analysis was conducted using grounded theory. Inductive coding was utilized, progressing through open, axial, and selective coding. Principal findings: Participants relied on community sources for information about the YF mass vaccination. Information was disseminated door-to-door, in community spaces, during religious gatherings, and on the radio. However, most respondents had no knowledge of the vaccine, and it was unclear to them whether a booster dose was required. In addition, the simultaneous presidential election during the mass vaccination campaign led to suspicion and resistance to vaccination. The lack of reliable and trustworthy information and the politicization of vaccination campaigns reinforced mistrust of YF vaccines. Conclusions/significance: People in remote areas affected by YF outbreaks rely on community sources of information. We therefore recommend improving health education, communication, and engagement through respected and trusted community members. Vaccination campaigns can never be seen as detached from political systems and power relations. Author summary: Yellow fever is transmitted by mosquitoes in tropical regions of South America and Africa. It can cause severe illness and death. Yellow fever can be prevented with a vaccine. However, people in several affected regions are not vaccinated because the vaccine is expensive and not part of routine immunization. For them, access to the vaccine is only possible during emergency mass vaccination campaigns when an outbreak occurs. In this study, we explored local perceptions of emergency yellow fever mass vaccination among vulnerable groups (people over 65 years and pregnant women) in Uganda to understand better how these people have access to vaccine information, what information reaches affected communities, what motivates people to be vaccinated, and what political motives may influence vaccination programs. Despite extensive campaigns, we found that the information reaching communities varied widely, with people relying heavily on community sources. In addition, the lack of trustworthy information and the politicization of vaccination campaigns increased mistrust of yellow fever vaccines. We also found that informed consent is only possible if the principle of vaccination—protection from disease—is understood. Awareness campaigns should focus on a broad understanding of the importance of immunization. Those involved in organizing campaigns should be aware of the potential impact of politicization on vaccine uptake. [ABSTRACT FROM AUTHOR]

Despite the significant success of India's COVID-19 vaccination program, a sizeable proportion of the adult population remains unvaccinated or has received a single dose of the vaccine. Despite the recommendations of the Government of India for the two doses of the COVID-19 vaccine and the precautionary booster dose, many people were still hesitant towards the COVID-19 full vaccination. Hence, this study aimed to identify the primary behavioral and psychological factors contributing to vaccine hesitancy. Cross-sectional data was collected via a multi-stage sampling design by using a scheduled sample survey in the Gorakhpur district of Uttar Pradesh, India, between 15 July 2022 to 30 September 2022. This study has utilized three health behavior models—the Health Belief Model (HBM), the Theory of Planned Behavior (TPB), and the 5C Psychological Antecedents of vaccination, and employed bivariate and multivariable binary logistic regression model to assess the level of vaccine hesitancy and predictive health behavior of the respondents. Results indicate that among the constructs of the HBM and 5C Antecedents models, "perceived benefits", "confidence" and "collective responsibility" showed a lesser likelihood of COVID-19 vaccine hesitancy. However, in the TPB model constructs, a 'negative attitude towards the vaccine' showed a four times higher likelihood of COVID-19 vaccine hesitancy. From the future policy perspective, this study suggested that addressing the issue of 'negative attitudes towards the vaccine' and increasing the trust or confidence for the vaccine through increasing awareness about the benefits of the vaccination in India may reduce vaccine hesitancy. [ABSTRACT FROM AUTHOR]

Background: Vaccination has been one of the most effective preventive strategies to contain the COVID-19 pandemic. However, as the COVID-19 vaccines' effect wanes off after some time and given their reduced level of protection against mutation strains of the virus, the calls for boosters and second boosters signal the need for continuous vaccination for the foreseeable future. As Malaysia transitions into the endemic phase, the nation's ability to co-exist with the virus in the endemic phase will hinge on people's continuance intention to be vaccinated against the virus. Adapting the expectations confirmation model (ECM) to the public health context and in a developing country, this study integrates the ECM with the health belief model (HBM) and the theory of reasoned action (TRA) to examine the inter-relationships of the predictors of people's continuance intention to vaccinate against COVID-19. Methodology: Data were collected using self-administered questionnaires from 1,914 respondents aged 18 and above by a marketing consulting firm via its online panel. The partial least squares structural equation modeling (PLS-SEM) technique was used to analyze the data. Results: Out of the 1,914 respondents, 55.9% reported having a continuance intention to vaccinate against COVID-19, similar to other developing countries. The multivariate analysis revealed that perceived usefulness and satisfaction significantly influenced individuals' continuance intention to vaccinate against COVID-19. Additionally, attitude was found to play a key role in influencing behavioral change among individuals towards their perceptions of continuously getting vaccinated against COVID-19. Conclusions: By integrating three theoretical frameworks (i.e., HBM, TRA and ECM), this study showed that behavioral characteristics could provide insights towards continuance vaccination intention. Hence, policymakers and key stakeholders can develop effective public health strategies or interventions to encourage vaccine booster uptake by targeting behavioral factors such as perceived usefulness, attitude, satisfaction, and subjective norms. [ABSTRACT FROM AUTHOR]

Influenza viruses cause epidemics and can cause pandemics with substantial morbidity with some mortality every year. Seasonal influenza vaccines have incomplete effectiveness and elicit a narrow antibody response that often does not protect against mutations occurring in influenza viruses. Thus, various vaccine approaches have been investigated to improve safety and efficacy. Here, we evaluate an mRNA influenza vaccine encoding hemagglutinin (HA) proteins in a BALB/c mouse model. The results show that mRNA vaccination elicits neutralizing and serum antibodies to each influenza virus strain contained in the current quadrivalent vaccine that is designed to protect against four different influenza viruses including two influenza A viruses (IAV) and two influenza B (IBV), as well as several antigenically distinct influenza virus strains in both hemagglutination inhibition assay (HAI) and virus neutralization assays. The quadrivalent mRNA vaccines had antibody titers comparable to the antibodies elicited by the monovalent vaccines to each tested virus regardless of dosage following an mRNA booster vaccine. Mice vaccinated with mRNA encoding an H1 HA had decreased weight loss and decreased lung viral titers compared to mice not vaccinated with an mRNA encoding an H1 HA. Overall, this study demonstrates the efficacy of mRNA-based seasonal influenza vaccines are their potential to replace both the currently available split-inactivated, and live-attenuated seasonal influenza vaccines. [ABSTRACT FROM AUTHOR]

Background: Understanding the immune response kinetics to SARS-CoV-2 infection and COVID-19 vaccination is important in nursing home (NH) residents, a high-risk population. Methods: An observational longitudinal evaluation of 37 consenting vaccinated NH residents with/without SARS-CoV-2 infection from October 2020 to July 2022 was conducted to characterize the immune response to spike protein due to infection and/or mRNA COVID-19 vaccine. Antibodies (IgG) to SARS-CoV-2 full-length spike, nucleocapsid, and receptor binding domain protein antigens were measured, and surrogate virus neutralization capacity was assessed using Meso Scale Discovery immunoassays. The participant's spike exposure status varied depending on the acquisition of infection or receipt of a vaccine dose. Longitudinal linear mixed effects modeling was used to describe trajectories based on the participant's last infection or vaccination; the primary series mRNA COVID-19 vaccine was considered two spike exposures. Mean antibody titer values from participants who developed an infection post receipt of mRNA COVID-19 vaccine were compared with those who did not. In a subset of participants (n = 15), memory B cell (MBC) S-specific IgG (%S IgG) responses were assessed using an ELISPOT assay. Results: The median age of the 37 participants at enrollment was 70.5 years; 30 (81%) had prior SARS-CoV-2 infection, and 76% received Pfizer-BioNTech and 24% Moderna homologous vaccines. After an observed augmented effect with each spike exposure, a decline in the immune response, including %S IgG MBCs, was observed over time; the percent decline decreased with increasing spike exposures. Participants who developed an infection at least two weeks post-receipt of a vaccine were observed to have lower humoral antibody levels than those who did not develop an infection post-receipt. Conclusions: These findings suggest that understanding the durability of immune responses in this vulnerable NH population can help inform public health policy regarding the timing of booster vaccinations as new variants display immune escape. [ABSTRACT FROM AUTHOR]

Background: The Australian Government implemented a national vaccination campaign against COVID-19 beginning February 22, 2021. The roll-out was criticised for being delayed relative to many high-income countries, but high levels of vaccination coverage were belatedly achieved. The large-scale Omicron outbreak in January 2022 resulted in a massive number of cases and deaths, although mortality would have been far higher if not for vigorous efforts to rapidly vaccinate the entire population. The impact of the vaccination coverage was assessed over this extended period. Methods: We considered NSW, as the Australian jurisdiction with the highest quality data for our purposes and which still reflected the national experience. Weekly death rates were derived among individuals aged 50+ with respect to vaccine status between August 8, 2021 and July 9, 2022. We evaluated deaths averted by the vaccination campaign by modelling alternative counterfactual scenarios based on a simple data-driven modelling methodology presented by Jia et al. (2023). Findings: Unvaccinated individuals had a 7.7-fold greater mortality rate than those who were fully vaccinated among people aged 50+, which rose to 11.2-fold in those who had received a booster dose. If NSW had fully vaccinated its ~2.9 million 50+ residents earlier (by July 28, 2021), only 440 of the total 3,495 observed 50+ deaths would have been averted. Up to July 9, 2022, the booster campaign prevented 1,860 deaths. In the absence of a vaccination campaign, ~21,250 COVID-19 50+ deaths (conservative estimate) could have been expected in NSW i.e., some 6 times the actual total. We also find the methodology of Jia et al. (2023) can sometimes significantly underestimate that actual number. Interpretation: The Australian vaccination campaign was successful in reducing mortality over 2022, relative to alternative hypothetical vaccination scenarios. The success was attributable to the Australian public's high levels of engagement with vaccination in the face of new SARS-COV-2 variants, and because high levels of vaccination coverage (full and booster) were achieved in the period shortly before the major Omicron outbreak of 2022. [ABSTRACT FROM AUTHOR]

Background: We previously demonstrated that when vaccines prevent infection, the dynamics of mixing between vaccinated and unvaccinated sub-populations is such that use of imperfect vaccines markedly decreases risk for vaccinated people, and for the population overall. Risks to vaccinated people accrue disproportionately from contact with unvaccinated people. In the context of the emergence of Omicron SARS-CoV-2 and evolving understanding of SARS-CoV-2 epidemiology, we updated our analysis to evaluate whether our earlier conclusions remained valid. Methods: We modified a previously published Susceptible-Infectious-Recovered (SIR) compartmental model of SARS-CoV-2 with two connected sub-populations: vaccinated and unvaccinated, with non-random mixing between groups. Our expanded model incorporates diminished vaccine efficacy for preventing infection with the emergence of Omicron SARS-CoV-2 variants, waning immunity, the impact of prior immune experience on infectivity, "hybrid" effects of infection in previously vaccinated individuals, and booster vaccination. We evaluated the dynamics of an epidemic within each subgroup and in the overall population over a 10-year time horizon. Results: Even with vaccine efficacy as low as 20%, and in the presence of waning immunity, the incidence of COVID-19 in the vaccinated subpopulation was lower than that among the unvaccinated population across the full 10-year time horizon. The cumulative risk of infection was 3–4 fold higher among unvaccinated people than among vaccinated people, and unvaccinated people contributed to infection risk among vaccinated individuals at twice the rate that would have been expected based on the frequency of contacts. These findings were robust across a range of assumptions around the rate of waning immunity, the impact of "hybrid immunity", frequency of boosting, and the impact of prior infection on infectivity in unvaccinated people. Interpretation: Although the emergence of the Omicron variants of SARS-CoV-2 has diminished the protective effects of vaccination against infection with SARS-CoV-2, updating our earlier model to incorporate loss of immunity, diminished vaccine efficacy and a longer time horizon, does not qualitatively change our earlier conclusions. Vaccination against SARS-CoV-2 continues to diminish the risk of infection among vaccinated people and in the population as a whole. By contrast, the risk of infection among vaccinated people accrues disproportionately from contact with unvaccinated people. [ABSTRACT FROM AUTHOR]

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, continues to mutate and generates new variants with increasingly severe immune escape, urging the upgrade of COVID-19 vaccines. Here, based on a similar dimeric RBD design as our previous ZF2001 vaccine, we developed a novel broad-spectrum COVID-19 mRNA vaccine, SWIM516, with chimeric Delta-BA.2 RBD dimer delivered by lipopolyplex (LPP). Unlike the popular lipid nanoparticle (LNP), this LPP-delivered mRNA expresses only in the injection site, which avoids potential toxicity to the liver. We demonstrated the broad-spectrum humoral and cellular immunogenicity of this vaccine to Delta and Omicron sub-variants in naïve mice and as booster shots. When challenged with Delta or Omicron live virus, vaccinated hACE2 transgenic mice and rhesus macaques were both protected, displaying significantly reduced viral loads and markedly relieved pathological damages. We believe the SWIM516 vaccine qualifies as a candidate for the next-generation broad-spectrum COVID-19 vaccine. Author summary: mRNA vaccines have demonstrated their advantages in immunogenicity and development speed during the coronavirus disease 2019 (COVID-19) pandemic. However, the significant immune escape caused by the evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presented a considerable challenge to the effectiveness of COVID-19 vaccines. Moreover, concerns have arisen about the potential liver toxicity associated with the lipid nanoparticles (LNP) used in approved mRNA vaccines, raising questions about their safety. To address these challenges, we have developed the SWIM516 vaccine, which utilizes a chimeric Delta-BA.2 RBD dimer immunogen to provide broad-spectrum protection and a lipopolyplex (LPP) delivery system to enhance safety. This vaccine has demonstrated its ability to induce broad-spectrum immunogenicity in mice and offers protection to both mice and monkeys when exposed to live SARS-CoV-2 challenges, qualifying it as a next-generation broad-spectrum COVID-19 vaccine. [ABSTRACT FROM AUTHOR]

Post vaccine immunity following COVID-19 mRNA vaccination may be driven by extrinsic, or controllable and intrinsic, or inherent health factors. Thus, we investigated the effects of extrinsic and intrinsic on the peak antibody response following COVID-19 primary vaccination and on the trajectory of peak antibody magnitude and durability over time. Participants in a longitudinal cohort attended visits every 3 months for up to 2 years following enrollment. At baseline, participants provided information on their demographics, recreational behaviors, and comorbid health conditions which guided our model selection process. Blood samples were collected for serum processing and spike antibody testing at each visit. Cross-sectional and longitudinal models (linear-mixed effects models) were generated to assess the relationship between selected intrinsic and extrinsic health factors on peak antibody following vaccination and to determine the influence of these predictors on antibody over time. Following cross-sectional analysis, we observed higher peak antibody titers after primary vaccination in females, those who reported recreational drug use, younger age, and prior COVID-19 history. Following booster vaccination, females and Hispanics had higher peak titers after the 3rd and 4th doses, respectively. Longitudinal models demonstrated that Moderna mRNA-1273 recipients, females, and those previously vaccinated had increased peak titers over time. Moreover, drug users and half-dose Moderna mRNA-1273 recipients had higher peak antibody titers over time following the first booster, while no predictive factors significantly affected post-second booster antibody responses. Overall, both intrinsic and extrinsic health factors play a significant role in shaping humoral immunogenicity after initial vaccination and the first booster. The absence of predictive factors for second booster immunogenicity suggests a more robust and consistent immune response after the second booster vaccine administration. [ABSTRACT FROM AUTHOR]

Background: During the SARS-CoV-2 testing program offered through the RT-PCR test by Sapienza University of Rome, we conducted a test-negative case-control study to identify risk factors for acquiring SARS-CoV-2 infection among university students. Methods: Each SARS-CoV-2-positive case detected was matched to two controls randomly selected from students who tested negative on the same day. 122 positive students and 244 negative students were enrolled in the study. Multivariable conditional logistic regression models were built. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. A second model was limited to students who had attended campus. Results: Out of 8223 tests for SARS-CoV-2, 173 students tested positive (2.1%), of whom 122 (71.5%) were included in the case-control study. In the first analysis, being a non-Italian student (aOR: 8.93, 95% CI: 2.71–29.41), having received only the primary vaccination course (aOR: 2.94, 95% CI: 1.24–6.96) compared to the booster dose, known exposure to a COVID-19 case or someone with signs/symptoms suggestive of COVID-19 (aOR: 6.51, 95% CI: 3.48–12.18), and visiting discos (aOR: 4.07, 95% CI: 1.52–10.90) in the two weeks before testing increased the likelihood of SARS-CoV-2 infection. Conversely, students attending in-person lectures on campus seemed less likely to become infected (aOR: 0.34, 95% CI: 0.15–0.77). No association was found with other variables. The results of the second model were comparable to the first analysis. Conclusions: This study indicates that if universities adopt strict prevention measures, it is safe for students to attend, even in the case of an infectious disease epidemic. [ABSTRACT FROM AUTHOR]

Background: Conducting a study in rural pre-dominant areas will help to understand the penetration of the vaccination campaign during the COVID-19 health crisis. This study aimed to investigate vaccination coverage against COVID-19 among the rural adult population in India and to identify factors associated with vaccination coverage. Methods: A population-based cross-sectional study was conducted among the rural population in one district of north India from January to February 2023. A semi-structured questionnaire was designed on the SurveyMonkey digital platform for interviewing the participants, which consisted of questions related to socio-demographic profile, health problems, vaccination status, types of vaccine, re-infection after vaccination, and functional difficulties. The data regarding infection with COVID-19 was collected based on self-reported positive testing for SARS-CoV 2 on RT-PCR. Findings: A total of 3700 eligible individuals were enumerated for the survey, out of which 2954 (79.8%) were interviewed. The infection rate of past COVID-19 infection, based on self-report of testing positive, was 6.2% (95%CI: 5.3–7.1). Covishield vaccine was received by most participants (81.3%, 2380) followed by Covaxin (12.3%, 361) and Pfizer manufactured vaccine (0.03,1). The coverage for first, second, and booster doses of the vaccine was 98.2% (2902), 94.8% (2802), and 10.7% (315) respectively. The risk of reinfection at 12 months or more among participants with two doses of vaccine was 1.6% (46/2802, 95%CI: 1.2–2.1). The coverage among those with severe functional difficulties was lesser as compared to those with some or no difficulties. Interpretation: Vaccination coverage against COVID-19 in rural Haryana, India is not dependent on factors like gender or occupation but is dependent on age and education. Although the full and partial vaccination coverage is high, the booster dose coverage is poor. In addition, the presence of severe disability was significantly associated with reduced vaccination coverage. [ABSTRACT FROM AUTHOR]

Background: Latine communities in the United States have been disproportionately affected by COVID-19. It is critical to gain a better understanding of the sociocultural determinants that challenge and facilitate COVID-19 testing, vaccination, and booster uptake within these vulnerable communities to inform culturally congruent strategies and interventions. Methods: In summer 2022, our community-based participatory research partnership conducted 30 key informant interviews and 7 focus groups with 64 Spanish-speaking Latine participants in North Carolina. Interviewees consisted of representatives from health and service organizations, most of whom were engaged with direct service to Spanish speakers. Interviews were conducted in either English or Spanish, depending on the preference of the participant; all focus groups were conducted in Spanish. Interviews and focus groups were conducted in person or by videoconference. Results: Twenty themes emerged that we organize into four domains: general perceptions about COVID-19; barriers to COVID-19 testing, vaccination, and booster uptake; facilitators to COVID-19 testing, vaccination, and booster uptake; and recommendations to promote testing, vaccination, and booster uptake. Discussion: Results underscore important sociocultural determinants of ongoing COVID-19 testing, vaccination, and booster uptake to consider in developing interventions for Spanish-speaking Latines in the United States. Based on this formative work, our partnership developed Nuestra Comunidad Saludable (Our Healthy Community). We are implementing the intervention to test whether trained peer navigators can increase COVID-19 testing, vaccination, and booster uptake among Spanish-speaking Latines through blending in-person interactions and mHealth (mobile health) strategies using social media. [ABSTRACT FROM AUTHOR]

Background: Evidence on protection of different patterns of infection- and vaccine-acquired immunity against Omicron-associated severe illness is useful in planning booster vaccination strategies. We examined protection of prior SARS-CoV-2 infection, a third or a fourth COVID-19 vaccine dose, and hybrid immunity against Omicron-associated severe illness. Methods and findings: This population-based cohort study followed five million individuals with at least one SARS-CoV-2 RT-PCR test before November 21, 2021 until an Omicron-associatedhospitalization or death. We used Cox regression models to estimate risks of Omicron-associated hospitalization and a composite severe outcome (hospitalized and death), among individuals with infection- and/or vaccination-acquired immunity. Individuals who were unvaccinated and had no history of a prior infection severed as the reference group. Both adjusted hazard ratios (HR) and corresponding protection (one minus adjusted HR), with 95% confidence intervals (CIs), were reported. Three doses provided 94% (95%CI 93–95) and 93% (95%CI 91–94) protection against Omicron-associated hospitalization at 2–3 and ≥3 months post-vaccination respectively, similar to the protection conferred by three doses and a prior infection (2–3 months: 99%, 95%CI 97–100; ≥3 months: 97%, 95%CI 92–99) and four doses (1 month: 87%, 95%CI 79–92; 1–2 months: 96%, 95%CI 92–98). In individuals ≥65 years old, protection of four doses increased to 95% (95%CI 91–98) at 1–2 months, significantly higher than that of three doses over the follow-up period. Similar results were observed with the composite severe outcome. Conclusion: At least three antigenic exposures, achieved by vaccination or infection, confers significant protection against Omicron-associated hospitalization and death in all age groups. Our findings support a third dose for the overall population, regardless of prior infection status, and a fourth dose for the elderly to maintain high level of immunity and substantially reduce risk of severe illness at individual level. [ABSTRACT FROM AUTHOR]

COVID-19 vaccination has significantly decreased morbidity, hospitalizations, and death during the pandemic. However, disparities in vaccination uptake threatens to stymie the progress made in safeguarding the health of Americans. Using a nationally representative adult (≥18 years old) sample from the 2021 Medical Expenditure Panel Survey (MEPS), we aimed to explore disparities in COVID-19 vaccine and booster uptake by income levels. To reflect the nature of the survey, a weighted logistic regression analysis was used to explore factors associated with COVID-19 vaccine and booster uptake. A total of 241,645,704 (unweighted n = 21,554) adults were included in the analysis. Average (SD) age of the population was 49 (18) years old, and 51% were female. There were disparities in COVID-19 vaccine and booster uptake by income groups. All other income groups were less likely to receive COVID-19 vaccines and booster shot than those in the high-income group. Those in the poor income group had 55% lower odds of being vaccinated for COVID-19 (aOR = 0.45, p<0.01). Considering the female population only, women with lower incomes may have greater disparities in access to COVID-19 vaccines than do males with lower incomes. Disparities in COVID-19 vaccination by income may have even greater implications as the updated vaccines are rolled out in the US without the government covering the cost as before. [ABSTRACT FROM AUTHOR]

In Quebec (Canada), the roll-out of the vaccination started slowly in December 2020 due to limited vaccine supply. While the first and second doses were well-accepted among adults and vaccine uptake was above 90%, in late 2021 and 2022, vaccine acceptance decreased for children vaccination and receipt of a 3rd or a 4th dose. In the autumn of 2022, four focus groups were conducted with vaccine-hesitant parents of children aged 0–4 and adults who expressed little intention to receive a booster dose. The objective of this study was to gather participants' perspectives on vaccination in general, on the COVID-19 vaccination campaign and the information available, and to gain insights into the underlying reasons for their low intention of either having their child(ren) vaccinated, or receiving an additional dose of vaccine. A total of 35 participants took part in the focus groups. While participants expressed a certain level of trust and confidence in public health and government authorities regarding pandemic management and the vaccination campaign, they were also concerned that transparent information was lacking to support an informed decision on booster doses and children's vaccination. Many participants felt adequately protected against the infection during the focus groups, citing a lack of perceived benefits as the primary reason for refusing a booster dose. Parents who refused to administer the COVID-19 vaccine to their young children felt that the vaccine was not useful for children and were concerned about potential side effects. The majority reported that their opinions regarding other recommended vaccines had not changed since the beginning of the pandemic. While these results are reassuring, our findings highlight the importance of transparency in public health communications about vaccines to increase confidence and to develop strategies to address vaccine fatigue and complacency toward COVID-19 vaccines. [ABSTRACT FROM AUTHOR]

The 2022 FIFA World Cup was the first major multi-continental sporting Mass Gathering Event (MGE) of the post COVID-19 era to allow foreign spectators. Such large-scale MGEs can potentially lead to outbreaks of infectious disease and contribute to the global dissemination of such pathogens. Here we adapt previous work and create a generalisable model framework for assessing the use of disease control strategies at such events, in terms of reducing infections and hospitalisations. This framework utilises a combination of meta-populations based on clusters of people and their vaccination status, Ordinary Differential Equation integration between fixed time events, and Latin Hypercube sampling. We use the FIFA 2022 World Cup as a case study for this framework (modelling each match as independent 7 day MGEs). Pre-travel screenings of visitors were found to have little effect in reducing COVID-19 infections and hospitalisations. With pre-match screenings of spectators and match staff being more effective. Rapid Antigen (RA) screenings 0.5 days before match day performed similarly to RT-PCR screenings 1.5 days before match day. Combinations of pre-travel and pre-match testing led to improvements. However, a policy of ensuring that all visitors had a COVID-19 vaccination (second or booster dose) within a few months before departure proved to be much more efficacious. The State of Qatar abandoned all COVID-19 related travel testing and vaccination requirements over the period of the World Cup. Our work suggests that the State of Qatar may have been correct in abandoning the pre-travel testing of visitors. However, there was a spike in COVID-19 cases and hospitalisations within Qatar over the World Cup. Given our findings and the spike in cases, we suggest a policy requiring visitors to have had a recent COVID-19 vaccination should have been in place to reduce cases and hospitalisations. Author summary: Mass Gathering Events (MGEs) can potentially lead to outbreaks of infectious disease and facilitate the dissemination of such pathogens. We have adapted previous work to create a framework for simulating disease transmission and mitigation at such MGEs. We use the 2022 FIFA World Cup as a test case for this framework (modelling each match as independent 7 day MGEs). A policy of Pre-travel screenings of visitors was found to have little effect in reducing COVID-19 cases and hospitalisations. Pre-match screenings of spectators and match staff was found to be more effective. The most effective policy was to ensure that all visitors had a COVID-19 vaccination (second or booster dose) within a few months before departure. Qatar abandoned all COVID-19 related travel testing and vaccination requirements over the period of the World Cup. Our work suggests that the State of Qatar may have been correct in abandoning the pre-travel testing of visitors. However, there was a spike in COVID-19 cases and hospitalisations within Qatar over the World Cup. Given our findings and the spike in cases, we suggest a policy requiring visitors to have had a recent COVID-19 vaccination should have been in place to reduce cases and hospitalisations. [ABSTRACT FROM AUTHOR]

Human adenovirus (HAdV), particularly the HAdV type 5 (HAdV-5), has been extensively utilized in the development of vector vaccines due to its high immunogenicity, good safety profile, and ease of propagation. However, one of the main challenges in its use is the presence of pre-existing immunity among vaccine recipients. Pre-existing neutralizing antibodies (NAbs) can prevent the uptake of HAdV-5 vectors and reduce vaccine efficacy. Hence, this study investigated the seroprevalence of NAbs against HAdV-5 in urban and rural regions of the Philippines. Luciferase-based neutralization assay was performed on 391 plasma/serum samples. Out of these samples, 346 or 88.5% were positive for HAdV-5 NAbs, and the majority of them (56.8%) had high titers against the virus. Among the regions included in this study, Bicol (Region V) had the highest seroprevalence rate (94.1%). Our findings show that a significant number of adults in the Philippines have pre-existing immunity against HAdV-5. This supports the recommendation that vaccination programs in the country should consider implementing vaccination techniques, such as a prime-boost regimen or addition of booster doses, to address the potential negative effects of pre-existing HAdV-5 immunity in the efficacy of adenoviral vector-based vaccines. [ABSTRACT FROM AUTHOR]

Background: Vaccines have reduced severe disease and death from Coronavirus Disease 2019 (COVID-19). However, with evidence of waning efficacy coupled with continued evolution of the virus, health programmes need to evaluate the requirement for regular booster doses, considering their impact and cost-effectiveness in the face of ongoing transmission and substantial infection-induced immunity. Methods and findings: We developed a combined immunological-transmission model parameterised with data on transmissibility, severity, and vaccine effectiveness. We simulated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and vaccine rollout in characteristic global settings with different population age-structures, contact patterns, health system capacities, prior transmission, and vaccine uptake. We quantified the impact of future vaccine booster dose strategies with both ancestral and variant-adapted vaccine products, while considering the potential future emergence of new variants with modified transmission, immune escape, and severity properties. We found that regular boosting of the oldest age group (75+) is an efficient strategy, although large numbers of hospitalisations and deaths could be averted by extending vaccination to younger age groups. In countries with low vaccine coverage and high infection-derived immunity, boosting older at-risk groups was more effective than continuing primary vaccination into younger ages in our model. Our study is limited by uncertainty in key parameters, including the long-term durability of vaccine and infection-induced immunity as well as uncertainty in the future evolution of the virus. Conclusions: Our modelling suggests that regular boosting of the high-risk population remains an important tool to reduce morbidity and mortality from current and future SARS-CoV-2 variants. Our results suggest that focusing vaccination in the highest-risk cohorts will be the most efficient (and hence cost-effective) strategy to reduce morbidity and mortality. In a modelling study, Alexandra Hogan and colleagues investigate long term vaccination strategies to mitigate the impact of SARS-CoV-2 transmission. Author summary: Why was this study done?: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus causing Coronavirus Disease 2019 (COVID-19), is now endemic globally. Vaccination remains important to reduce hospitalisations and deaths. Health authorities need to consider how frequently booster doses will be required and in which age groups. They also need to know the additional value of switching to vaccines that have been adapted to match more recently circulating variants of concern. What did the researchers do and find?: We developed a mathematical model that captures the continued circulation and evolution of the SARS-CoV-2 virus in the presence of widespread infection-induced immunity from past exposure as well as vaccine-induced immunity from primary vaccination campaigns in 2021/2022. We used the model to explore different strategies for continued vaccination including the age group targeted, the frequency of boosting, and whether the vaccine was adapted to match more recent variants. In both high-income and low-middle-income settings, regardless of whether there was a high level of transmission in 2020/21 or a zero-COVID policy, we found that the most cost-effective vaccination strategy was to boost those at highest risk. We found that the current variant-adapted vaccines could avert nearly twice as many hospitalisations and deaths compared to the ancestral vaccines, and that updating these vaccines each year—as is done for seasonal influenza—could avert a further 30% of hospitalisations and deaths. What do these findings mean?: Continued booster vaccinations will remain important to reduce both hospitalisations and deaths but should be targeted towards the highest risk groups. The estimates provided here can help to inform discussions around value for money by comparing the cost-effectiveness of COVID-19 vaccination to other health programmes. The precise values are limited by uncertainty as to whether the virus will continue to evolve, whether any new variants may emerge, and the additional protection provided by further booster doses given the widespread exposure of the population to infection. [ABSTRACT FROM AUTHOR]

The impact of previous SARS-CoV-2 infection on the durability of Ad26.COV2.S vaccine-elicited responses, and the effect of homologous boosting has not been well explored. We followed a cohort of healthcare workers for 6 months after receiving the Ad26.COV2.S vaccine and a further one month after they received an Ad26.COV2.S booster dose. We assessed longitudinal spike-specific antibody and T cell responses in individuals who had never had SARS-CoV-2 infection, compared to those who were infected with either the D614G or Beta variants prior to vaccination. Antibody and T cell responses elicited by the primary dose were durable against several variants of concern over the 6 month follow-up period, regardless of infection history. However, at 6 months after first vaccination, antibody binding, neutralization and ADCC were as much as 59-fold higher in individuals with hybrid immunity compared to those with no prior infection. Antibody cross-reactivity profiles of the previously infected groups were similar at 6 months, unlike at earlier time points, suggesting that the effect of immune imprinting diminishes by 6 months. Importantly, an Ad26.COV2.S booster dose increased the magnitude of the antibody response in individuals with no prior infection to similar levels as those with previous infection. The magnitude of spike T cell responses and proportion of T cell responders remained stable after homologous boosting, concomitant with a significant increase in long-lived early differentiated CD4 memory T cells. Thus, these data highlight that multiple antigen exposures, whether through infection and vaccination or vaccination alone, result in similar boosts after Ad26.COV2.S vaccination. Author summary: A single dose of the adenovirus vector-based Ad26.COV2.S vaccine has been shown to induce durable immune responses which last months after administration. However, the impact of prior infection with distinct SARS-CoV-2 variants on antibody and T cell immune response durability has not been described in detail. In this study, we assessed antibody and T cell responses elicited by Ad26.COV2.S vaccination for 6 months after the initial dose in healthcare workers who either had no prior SARS-CoV-2 infection, or who had previously been infected with either the D614G or Beta variant. Immune responses were durable for up to 6 months after a single Ad26.COV2.S vaccination. However, antibody responses were significantly higher in individuals with hybrid immunity compared to those with no prior infection. A homologous Ad26.COV2.S booster dose approximately 9 months after first vaccination increased the magnitude of the antibody responses to similar levels regardless of prior infection status. Boosting also expanded the proportion of early differentiated SARS-CoV-2 spike memory CD4 T cells. These data highlight the importance of a booster in individuals who only received a single Ad26.COV2.S dose. [ABSTRACT FROM AUTHOR]

Background: This study aimed at evaluation and comparison of PastoCovac Plus protein-subunit vaccine in parallel with ChAdOx1-S (AstraZeneca) and BBIBP-CorV (Sinopharm) in primarily vaccinated volunteers with two doses of ChAdOx1-S or BBIBP-CorV. Materials and methods: 194 volunteers enrolled the study who were previously primed with 2 doses of ChAdOx1-S or BBIBP-CorV vaccines. They were divided into two heterologous regimens receiving a third dose of PastoCovac Plus, and two parallel homologous groups receiving the third dose of BBIBP-CorV or ChAdOx1-S. Serum samples were obtained just before and 4 weeks after booster dose. Anti-spike IgG and neutralizing antibodies were quantified and the conventional live-virus neutralization titer, (cVNT50) assay was done against Omicron BA.5 variant. Moreover, the adverse events data were recorded after receiving booster doses. Results: ChAdOx1-S/PastoCovac Plus group reached 73.0 units increase in anti-Spike IgG rise compared to the ChAdOx1-S/ ChAdOx1-S (P: 0.016). No significant difference was observed between the two groups regarding neutralizing antibody rise (P: 0.256), indicating equivalency of both booster types. Adjusting for baseline titers, the BBIBP-CorV/PastoCovac Plus group showed 135.2 units increase (P<0.0001) in anti-Spike IgG, and 3.1 (P: 0.008) unit increase in mean rise of neutralizing antibodies compared to the homologous group. Adjustment for COVID-19 history, age, underlying diseases, and baseline antibody titers increased the odds of anti-Spike IgG fourfold rise both in the ChAdOx1-S (OR: 1.9; P: 0.199) and BBIBP CorV (OR: 37.3; P< 0.0001) heterologous groups compared to their corresponding homologous arms. The odds of neutralizing antibody fourfold rise, after adjustment for the same variables, was 2.4 (P: 0.610) for the ChAdOx1-S heterologous group and 5.4 (P: 0.286) for the BBIBP CorV heterologous groups compared to their corresponding homologous groups. All the booster types had the potency to neutralize BA.5 variant with no significant difference. The highest rate of adverse event incidence was recorded for ChAdOx1-S homologous group. Conclusions: PastoCovac Plus booster application in primed individuals with BBIBP-CorV or ChAdOx1-S successfully increased specific antibodies' levels without any serious adverse events. This vaccine could be administrated in the heterologous regimen to effectively boost humoral immune responses. Author summary: PastoCovac Plus is a protein subunit vaccine against COVID-19 which has been assessed highly immunogenic in the conducted clinical trials. According to SARS-CoV-2 ability to escape the immune system, booster doses have been recommended. It has been supposed that a booster of a different type could induce the immune responses stronger than the same priming vaccine series. In the present study, we evaluated PastoCovac Plus protein subunit vaccine as heterologous vaccine regimen in individuals who were primarily immunized with AstraZeneca (Adenovirus-based vaccine) or Sinopharm (inactivated virus-based vaccine) in parallel with the individuals who received a booster of the same priming vaccine (homologous groups). The results showed the great immunogenicity of PastoCovac Plus as a booster dose and increased both anti-Spike IgG and neutralizing antibodies' levels with no serious adverse event. Moreover, the applied booster vaccine successfully neutralized SARS-CoV-2 (Omicron BA.5 variant) through the test. Thus, the findings support mix-and-match strategy regarding COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Background: Cystic echinococcosis (CE) is caused by the infection of Echinococcus granulosus sensu lato (E. granulosus s.l.), one of the most harmful zoonotic helminths worldwide. Infected dogs are the major source of CE transmission. While praziquantel-based deworming is a main measure employed to control dog infections, its efficacy is at times compromised by the persistent high rate of dog re-infection and the copious discharge of E. granulosus eggs into the environment. Therefore, the dog vaccine is a welcome development, as it offers a substantial reduction in the biomass of E. granulosus. This study aimed to use previous insights into E. granulosus functional genes to further assess the protective efficacy of six recombinant proteins in dogs using a two-time injection vaccination strategy. Methods: We expressed and combined recombinant E. granulosus triosephosphate isomerase (rEgTIM) with annexin B3 (rEgANXB3), adenylate kinase 1 (rEgADK1) with Echinococcus protoscolex calcium binding protein 1 (rEgEPC1), and fatty acid-binding protein (rEgFABP) with paramyosin (rEgA31). Beagle dogs received two subcutaneous vaccinations mixed with Quil-A adjuvant, and subsequently orally challenged with protoscoleces two weeks after booster vaccination. All dogs were sacrificed for counting and measuring E. granulosus tapeworms at 28 days post-infection, and the level of serum IgG was detected by ELISA. Results: Dogs vaccinated with rEgTIM&rEgANXB3, rEgADK1&rEgEPC1, and rEgFABP-EgA31 protein groups exhibited significant protectiveness, with a worm reduction rate of 71%, 57%, and 67%, respectively, compared to the control group (P < 0.05). Additionally, the vaccinated groups exhibited an inhibition of worm growth, as evidenced by a reduction in body length and width (P < 0.05). Furthermore, the level of IgG in the vaccinated dogs was significantly higher than that of the control dogs (P < 0.05). Conclusion: These verified candidates may be promising vaccines for the prevention of E. granulosus infection in dogs following two injections. The rEgTIM&rEgANXB3 co-administrated vaccine underscored the potential for the highest protective efficacy and superior protection stability for controlling E. granulosus infections in dogs. Author summary: Cystic echinococcosis (CE), a neglected parasitic zoonosis of global health significance, poses a persistent threat to humans and imposes substantial economic burdens. Dogs are the main source for human CE infections, although the implementation of praziquantel-based deworming programs targeting dogs, certain regions continue to experience high human CE incidence, highlighting the need for alternative preventive strategies such as dog vaccines. Various recombinant vaccines have exhibited promising efficacy; however, no commercially licensed vaccines are currently available for field use due to two key challenges. Firstly, the existing dog vaccine immunization regimen necessitates three injections to achieve adequate protection. Secondly, the vaccine's protective efficacy displays considerable variability among the dogs in vaccinated groups. To address these limitations, we employed the Escherichia coli expression system to produce six potential vaccine candidates. Additionally, we introduced a novel immune protocol involving a two-protein combined vaccine administered via a two-time injection in dogs. Employing this immunization protocol, the rEgTIM&rEgANXB3 co-administrated vaccine demonstrated exceptional stability, exhibiting minimal standard deviation and resulting in a notable 71% reduction in worm burden. Implementation of this two-protein combined vaccine with only two injections not only mitigates the CE infection risk to human and livestock but also represents the more cost-effective and practical solution ever for dog owners. [ABSTRACT FROM AUTHOR]

Coronavirus Disease 2019 (COVID-19) vaccination in Indonesia has shown effectiveness in reducing the morbidity and mortality of Covid-19. The study aims to evaluate the incidence rate and severity of Adverse Events Following Immunization (AEFI) of inactivated SARS-CoV-2 vaccine during the first quarter of 2021 until the second quarter of 2022 in Indonesia. More than two hundred million Sinovac/CoronaVac were given from January 13th, 2021, until June 30th, 2022. Data for this study were collected manually and electronically from the national vaccine safety website managed by the National Committee (NC) of AEFI Indonesia and the Ministry of Health Indonesia. The total number of injections observed in the study was 264,311,992 doses consisting of 142,449,795 (first dose), 121,613,324 (second dose), and 248,873 (booster dose). Of the injections given, 301 subjects with Serious AEFIs (SAE) and 10.261 subjects with non-serious AEFIs (AE) reported, with a majority of SAE and AEs found in the first dose. Most of the SAEs were classified as coincidental events by the NC AEFI (IR 0.8/1 million doses on first dose injection; 0.31 on second dose injection). ISRR (immunization stress-related response) is in the second rank of SAEs reported (0.59 IR/1 million doses on the first dose; 0.14 on the second dose). The incidence rate of SAEs and AEs, both in the variable of age, sex, and symptoms per 1 million dose injections in Indonesia, was very rare according to WHO guidelines. Most SAEs were classified as coincidences or unrelated to the vaccine. The result showed that the Sinovac/CoronaVac in Indonesia is safe. [ABSTRACT FROM AUTHOR]

Introduction: Taiwan introduced a two-dose inactivated Japanese encephalitis (JE) mouse brain-derived (JE-MB) vaccine into routine childhood immunization in 1968, with booster vaccination implemented in 1974 and 1983. In 2017, JE-MB vaccine was replaced by a two-dose live-attenuated chimeric vaccine (JE-CV). After implementation of JE vaccination programs, JE cases have shifted from children to adults. In this study, we described the JE epidemiology and identify high-risk groups to further inform vaccine policy. Methodology/Principal findings: We extracted data from Taiwan's notifiable disease surveillance database, vital statistics, and employment statistics from 2010 to 2022. Diagnosis of JE was confirmed by JE seroconversion, a four-fold increase in virus-specific antibodies, a positive JE viral nucleic-acid test, or JE virus isolation. From 2010 to 2022, a total of 313 cases of JE were diagnosed, resulting in an overall incidence rate of 0.10 cases per 100,000 person-years and a mortality rate of 0.006 per 100,000 population per year. Among these patients, 64% were male, and the median age was 51 years (range 0–82). Compared with people born in or after 1976 (vaccinated with four doses of JE-MB vaccine or two doses of JE-CV), those born in or before 1962 (unvaccinated) and those born during 1963–1975 (vaccinated with two or three doses of JE-MB vaccine) had a 4.2-fold (95% confidence interval [CI] 3.0–5.7) and 5.9-fold (95% CI 4.3–8.1) higher risk of JE, respectively. The relative risk of working in agriculture, forestry, fishing, or animal husbandry, compared to other occupations, was 5.0 (95% CI 3.5–7.0). Conclusions/Significance: In Taiwan, individuals born before 1976 and those employed in agriculture, forestry, fishing, or animal husbandry had a higher risk of JE. We recommend JE vaccination for people in these high-risk groups who have not been fully vaccinated or have an unknown vaccination history. Author summary: The Japanese encephalitis (JE) virus is primarily transmitted through infected mosquito bites between animals such as pigs and birds, with humans being the dead-end hosts. JE can lead to death or long-term neurological or psychiatric complications. Vaccination is the most effective preventive measure against JE. With the implementation of comprehensive immunization programs against JE since 1960s, Taiwan has experienced a significant decline in the incidence and mortality rates of the disease. This retrospective observational cohort study utilized Taiwan's national databases from 2010 to 2022 to investigate the epidemiology of JE and identify high-risk populations, thereby to inform vaccine policy. A total of 313 JE cases were diagnosed among Taiwanese citizens with an incidence rate of 0.10 cases per 100,000 person-years and a mortality rate of 0.006 per 100,000 population per year, indicating consistently low incidence and mortality rates. Several factors were statistically significantly associated with the occurrence of JE, including male gender, individuals born before 1976, residing outside the northern region, and working in occupations related to agriculture, forestry, fishing, or animal husbandry. To prevent JE, it is recommended to offer vaccination to high-risk populations who have not completed their immunization. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 Omicron variants have the potential to impact vaccine effectiveness and duration of vaccine-derived immunity. We analyzed U.S. multi-jurisdictional COVID-19 vaccine breakthrough surveillance data to examine potential waning of protection against SARS-CoV-2 infection for the Pfizer-BioNTech (BNT162b) primary vaccination series by age. Methods: Weekly numbers of SARS-CoV-2 infections during January 16, 2022–May 28, 2022 were analyzed by age group from 22 U.S. jurisdictions that routinely linked COVID-19 case surveillance and immunization data. A life table approach incorporating line-listed and aggregated COVID-19 case datasets with vaccine administration and U.S. Census data was used to estimate hazard rates of SARS-CoV-2 infections, hazard rate ratios (HRR) and percent reductions in hazard rate comparing unvaccinated people to people vaccinated with a Pfizer-BioNTech primary series only, by age group and time since vaccination. Results: The percent reduction in hazard rates for persons 2 weeks after vaccination with a Pfizer-BioNTech primary series compared with unvaccinated persons was lowest among children aged 5–11 years at 35.5% (95% CI: 33.3%, 37.6%) compared to the older age groups, which ranged from 68.7%–89.6%. By 19 weeks after vaccination, all age groups showed decreases in the percent reduction in the hazard rates compared with unvaccinated people; with the largest declines observed among those aged 5–11 and 12–17 years and more modest declines observed among those 18 years and older. Conclusions: The decline in vaccine protection against SARS-CoV-2 infection observed in this study is consistent with other studies and demonstrates that national case surveillance data were useful for assessing early signals in age-specific waning of vaccine protection during the initial period of SARS-CoV-2 Omicron variant predominance. The potential for waning immunity during the Omicron period emphasizes the importance of continued monitoring and consideration of optimal timing and provision of booster doses in the future. [ABSTRACT FROM AUTHOR]

Exosomes are emerging as potent and safe delivery carriers for use in vaccinology and therapeutics. A better vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to provide improved, broader, longer lasting neutralization of SARS-CoV-2, a more robust T cell response, enable widespread global usage, and further enhance the safety profile of vaccines given the likelihood of repeated booster vaccinations. Here, we use Capricor's StealthXTM platform to engineer exosomes to express native SARS-CoV-2 spike Delta variant (STX-S) protein on the surface for the delivery of a protein-based vaccine for immunization against SARS-CoV-2 infection. The STX-S vaccine induced a strong immunization with the production of a potent humoral immune response as demonstrated by high levels of neutralizing antibody not only against the delta SARS-CoV-2 virus but also two Omicron variants (BA.1 and BA.5), providing broader protection than current mRNA vaccines. Additionally, both CD4+ and CD8+ T cell responses were increased significantly after treatment. Quantification of spike protein by ELISA showed that only nanograms of protein were needed to induce a potent immune response. This is a significantly lower dose than traditional recombinant protein vaccines with no adjuvant required, which makes the StealthXTM exosome platform ideal for the development of multivalent vaccines with a better safety profile. Importantly, our exosome platform allows novel proteins, or variants in the case of SARS-CoV-2, to be engineered onto the surface of exosomes in a matter of weeks, comparable with mRNA vaccine technology, but without the cold storage requirements necessary for mRNA vaccines. The ability to utilize exosomes for cellular delivery of proteins, as demonstrated by STX-S, has enormous potential to revolutionize vaccinology by rapidly facilitating antigen presentation at an extremely low dose resulting in a potent, broad antibody response. [ABSTRACT FROM AUTHOR]

Introduction: The Delta variant has led to a surge in COVID-19 cases in Libya, making it crucial to investigate the impact of vaccination on mortality rates among hospitalized patients and the critically ill. This study aimed to explore the risk factors for COVID-19 mortality and the mortality rates among unvaccinated and vaccinated adults during the Delta wave who were admitted to a single COVID-19 care center in Tripoli, Libya. Methods: The study involved two independent cohorts (n = 341). One cohort was collected retrospectively from May 2021-August 2021 and the second cohort was prospectively collected from August 2021-October 2021. Most of the patients in the study became ill during the Delta wave. The two cohorts were merged and analysed as one group. Results: Most patients were male (60.5%) and 53.3% were >60 years old. The vast majority of patients did not have a previous COVID-19 infection (98.9%) and were unvaccinated (90.3%). Among vaccinated patients, 30 had received one dose of vaccine and only 3 had received two doses. Among patients who received one dose, 58.1% (18/31) died and 41.9% (13/31) survived. Most patients (72.2%) had a pre-existing medical condition. A multivariable prediction model showed that age >60 years was significantly associated with death (odds ratio = 2.328, CI 1.5–3.7, p-value = <0.0001). Conclusion: Our results indicate that previous infection or full vaccination against COVID-19 significantly reduces hospitalization and death. However, a single vaccine dose may not be adequate, especially for older individuals and those with underlying medical conditions. High-risk older patients with comorbidities should be fully vaccinated and offered up to date bivalent COVID-19 booster doses. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, many residents of high-income countries (HICs) were eligible for COVID-19 vaccine boosters, while many residents of lower-income countries (LICs) had not yet received a first dose. HICs made some efforts to contribute to COVID-19 vaccination efforts in LICs, but these efforts were limited in scale. A new literature discusses the normative importance of an international redistribution of vaccines. Our analysis contributes an empirical perspective on the willingness of citizens in a HIC to contribute to such efforts (which we term international vaccine solidarity). We analyse the levels and predictors of international vaccine solidarity. We surveyed a representative sample of German adults (n = 2019) who participated in a two-wave YouGov online survey (w1: Sep 13–21, 2021 and w2: Oct 4–13, 2021). International vaccine solidarity is measured by asking respondents preferences for sharing vaccine supplies internationally versus using that supply as boosters for the domestic population. We examine a set of pre-registered hypotheses. Almost half of the respondents in our sample (48%) prioritize giving doses to citizens in less developed countries. A third of respondents (33%) prefer to use available doses as boosters domestically, and a fifth of respondents (19%) did not report a preference. In line with our hypotheses, respondents higher in cosmopolitanism and empathy, and those who support domestic redistribution exhibit more support for international dose-sharing. Older respondents (who might be more at risk) do not consistently show less support for vaccine solidarity. These results help us to get a better understanding of the way citizens' form preferences about a mechanism that redistributes medical supplies internationally during a global crisis. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this cohort study was to evaluate the relationship between anthropometric and body composition parameters and anti-SARS-CoV-2 IgG titers in a group of females who were vaccinated against COVID-19 with two doses of ChAdOx1 vaccine and then boosted with the BNT162b2 vaccine. Materials and methods: The study group consisted of 63 women. Basic demographic and clinical data were collected. To assess the anti-SARS-CoV-2 immunoglobulin G titers following the vaccination, five blood draws were performed: 1) before the first dose, 2) before the second dose, 3) 14–21 days after the primary vaccination, 4) before the booster, and 5) 21 days after the booster. Blood samples were analyzed using a two-step enzymatic chemiluminescent assay. Body mass index and body composition were evaluated using bioelectrical impedance analysis. To select the most distinguishing parameters and correlations between anthropometric and body composition parameters and anti-SARS-CoV-2 IgG titers, factor analysis using the Principal Component Analysis was conducted. Results: Sixty-three females (mean age: 46.52 years) who met the inclusion criteria were enrolled. 40 of them (63.50%) participated in the post-booster follow-up. After receiving two doses of the ChAdOx1 vaccine, the study group's anti-SARS-CoV-2 IgG titers were 67.19 ± 77.44 AU/mL (mean ± SD), whereas after receiving a heterologous mRNA booster, the level of anti-SARS-CoV-2 IgG titers was about three-times higher and amounted to 212.64 ± 146.40 AU/mL (mean ± SD). Our data shows that seropositivity, obesity, non-fat-related, and fat-related body composition parameters all had a significant effect on the level of IgG titer after a two-dose vaccination of ChAdOx1. However, only non-fat-related and fat-related body composition parameters had a significant effect on the IgG titer after booster vaccination. Conclusion: COVID-19 infection before the first dose of vaccination is not related to IgG titer after booster administration. Body composition has a significant effect on the production of anti-SARS-CoV-2 IgG after booster vaccination in females. [ABSTRACT FROM AUTHOR]

Maternal COVID-19 vaccination could protect infants who are ineligible for vaccine through antibody transfer during pregnancy and lactation. We measured the quantity and durability of SARS-CoV-2 antibodies in human milk and infant blood before and after maternal booster vaccination. Prospective cohort of lactating women immunized with primary and booster COVID-19 vaccines during pregnancy or lactation and their infants. Milk and blood samples from October 2021 to April 2022 were included. Anti-nucleoprotein (NP) and anti-receptor binding domain (RBD) IgG and IgA in maternal milk and maternal and infant blood were measured and compared longitudinally after maternal booster vaccine. Forty-five lactating women and their infants provided samples. 58% of women were anti-NP negative and 42% were positive on their first blood sample prior to booster vaccine. Anti-RBD IgG and IgA in milk remained significantly increased through 120–170 days after booster vaccine and did not differ by maternal NP status. Anti-RBD IgG and IgA did not increase in infant blood after maternal booster. Of infants born to women vaccinated in pregnancy, 74% still had positive serum anti-RBD IgG measured on average 5 months after delivery. Infant to maternal IgG ratio was highest for infants exposed to maternal primary vaccine during the second trimester compared to third trimester (0.85 versus 0.29; p<0.001). Maternal COVID-19 primary and booster vaccine resulted in robust and long-lasting transplacental and milk antibodies. These antibodies may provide important protection against SARS-CoV-2 during the first six months of life. [ABSTRACT FROM AUTHOR]

Background: An increased risk of myocarditis or pericarditis after priming with mRNA Coronavirus Disease 2019 (COVID-19) vaccines has been shown but information on the risk post-booster is limited. With the now high prevalence of prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we assessed the effect of prior infection on the vaccine risk and the risk from COVID-19 reinfection. Methods and findings: We conducted a self-controlled case series analysis of hospital admissions for myocarditis or pericarditis in England between 22 February 2021 and 6 February 2022 in the 50 million individuals eligible to receive the adenovirus-vectored vaccine (ChAdOx1-S) for priming or an mRNA vaccine (BNT162b2 or mRNA-1273) for priming or boosting. Myocarditis and pericarditis admissions were extracted from the Secondary Uses Service (SUS) database in England and vaccination histories from the National Immunisation Management System (NIMS); prior infections were obtained from the UK Health Security Agency's Second-Generation Surveillance Systems. The relative incidence (RI) of admission within 0 to 6 and 7 to 14 days of vaccination compared with periods outside these risk windows stratified by age, dose, and prior SARS-CoV-2 infection for individuals aged 12 to 101 years was estimated. The RI within 27 days of an infection was assessed in the same model. There were 2,284 admissions for myocarditis and 1,651 for pericarditis in the study period. Elevated RIs were only observed in 16- to 39-year-olds 0 to 6 days postvaccination, mainly in males for myocarditis. Both mRNA vaccines showed elevated RIs after first, second, and third doses with the highest RIs after a second dose 5.34 (95% confidence interval (CI) [3.81, 7.48]; p < 0.001) for BNT162b2 and 56.48 (95% CI [33.95, 93.97]; p < 0.001) for mRNA-1273 compared with 4.38 (95% CI [2.59, 7.38]; p < 0.001) and 7.88 (95% CI [4.02, 15.44]; p < 0.001), respectively, after a third dose. For ChAdOx1-S, an elevated RI was only observed after a first dose, RI 5.23 (95% CI [2.48, 11.01]; p < 0.001). An elevated risk of admission for pericarditis was only observed 0 to 6 days after a second dose of mRNA-1273 vaccine in 16 to 39 year olds, RI 4.84 (95% CI [1.62, 14.01]; p = 0.004). RIs were lower in those with a prior SARS-CoV-2 infection than in those without, 2.47 (95% CI [1.32,4.63]; p = 0.005) versus 4.45 (95% [3.12, 6.34]; p = 0.001) after a second BNT162b2 dose, and 19.07 (95% CI [8.62, 42.19]; p < 0.001) versus 37.2 (95% CI [22.18, 62.38]; p < 0.001) for mRNA-1273 (myocarditis and pericarditis outcomes combined). RIs 1 to 27 days postinfection were elevated in all ages and were marginally lower for breakthrough infections, 2.33 (95% CI [1.96, 2.76]; p < 0.001) compared with 3.32 (95% CI [2.54, 4.33]; p < 0.001) in vaccine-naïve individuals respectively. Conclusions: We observed an increased risk of myocarditis within the first week after priming and booster doses of mRNA vaccines, predominantly in males under 40 years with the highest risks after a second dose. The risk difference between the second and the third doses was particularly marked for the mRNA-1273 vaccine that contains half the amount of mRNA when used for boosting than priming. The lower risk in those with prior SARS-CoV-2 infection, and lack of an enhanced effect post-booster, does not suggest a spike-directed immune mechanism. Research to understand the mechanism of vaccine-associated myocarditis and to document the risk with bivalent mRNA vaccines is warranted. In a nationwide, self-controlled case series analysis conducted in England, Julia Stowe and colleagues investigate the effect of prior SARS CoV-2 infection on the risk of hospital admission for myocarditis or pericarditis after primary or booster vaccination and after a confirmed SARS-CoV-2 infection. Author summary: Why was this study done?: Primary and booster immunisation with mRNA Coronavirus Disease 2019 (COVID-19) vaccine have been associated with an increased risk of acute myocarditis. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection may itself cause myocarditis or pericarditis. However, the effect of prior vaccination on this risk, and on the risk after a reinfection, has not been investigated. What did the researchers do and find?: We conducted a nationwide study in England to assess the risk of hospital admission for myocarditis or pericarditis after primary or booster and the risk after a confirmed SARS-CoV-2 infection in those with and without a prior confirmed SARS-CoV-2 infection. Elevated risks of myocarditis were found up to 6 days after each of priming dose of the available mRNA vaccines (BNT162b2 and mRNA-1723) and after mRNA booster doses following a mRNA priming course but not after a priming course of the adenovirus-vectored vaccine ChAdOx1-S. The only elevated seen after the ChAdOx1-S vaccine was after the dose in 16 to 39 year olds. For both mRNA vaccines, elevated risks were found in those under 40 years old, predominantly in males, were highest after the second priming dose and were generally lower in those vaccinated after a prior SARS-CoV-2 infection. There was an elevated risk of myocarditis and pericarditis in the 27 days after a SARS-CoV-2 infection which was higher in ≥40 year olds than 16 to 39 year olds and was still present in those with a reinfection or who had been vaccinated before infection. What do these findings mean?: This study provides information for policy makers and those recommended to receive booster mRNA vaccines on the associated rare risk of myocarditis or pericarditis in a population with a high prevalence of prior SARS-CoV-2 infection. The lower risk after a booster than primary course, and the lower risk in vaccinees with a prior SARS-CoV-2 infection, does not suggest an immune-mediated mechanism directed at the spike protein. The greater risk associated with mRNA-1273 vaccines, which have a higher mRNA dose than BNT162b2 vaccines, and the substantially lower risk after the mRNA-booster which has half the mRNA content than used for priming, may be suggestive an mRNA dose-related mechanism but further work is required to determine this. [ABSTRACT FROM AUTHOR]

Introduction: Achieving high COVID-19 vaccine booster coverage is an ongoing global challenge. Health authorities need evidence about effective communication interventions to improve acceptance and uptake. This study aimed to test effects of persuasive messages about COVID-19 vaccine booster doses on intention to vaccinate amongst eligible adults in Australia. Methods: In this online randomised controlled trial, adult participants received one of four intervention messages or a control message. The control message provided information about booster dose eligibility. Intervention messages added to the control message, each using a different persuasive strategy, including: emphasising personal health benefits of booster doses, community health benefits, non-health benefits, and personal agency in choosing vaccination. After the intervention, participants answered items about COVID-19 booster vaccine intention and beliefs. Intervention groups were compared to the control using tests of two proportions; differences of ≥5 percentage points were deemed clinically significant. A sub-group analysis was conducted among hesitant participants. Results: Of the 487 consenting and randomised participants, 442 (90.8%) completed the experiment and were included in the analysis. Participants viewing messages emphasising non-health benefits had the highest intention compared to those who viewed the control message (percentage point diff: 9.0, 95% CI -0.8, 18.8, p = 0.071). Intention was even higher among hesitant individuals in this intervention group compared to the control group (percentage point diff: 15.6, 95% CI -6.0, 37.3, p = 0.150). Conversely, intention was lower among hesitant individuals who viewed messages emphasising personal agency compared to the control group (percentage point diff: -10.8, 95% CI -33.0, 11.4, p = 0.330), although evidence in support of these findings is weak. Conclusion: Health authorities should highlight non-health benefits to encourage COVID-19 vaccine booster uptake but use messages emphasising personal agency with caution. These findings can inform communication message development and strategies to improve COVID-19 vaccine booster uptake. Clinical trial registration: Registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622001404718); trial webpage: https://www.anzctr.org.au/ACTRN12622001404718.aspx [ABSTRACT FROM AUTHOR]

A SARS-CoV-2 DNA vaccine targeting the spike protein and delivered by jet injection, nCOV-S(JET), previously shown to protect wild-type and immunosuppressed Syrian hamsters (Mesocricetus auratus), was evaluated via two needle-free delivery methods in rhesus macaques (Macaca mulatta). The methods included intramuscular delivery of 2 mg per vaccination with the PharmaJet Stratis device and intradermal delivery of 0.4 mg per vaccination with the PharmaJet Tropis device. We hypothesized that the nCOV-S(JET) vaccine would mount detectable neutralizing antibody responses when delivered by needle-free jet injection by either the intradermal or intramuscular route. When delivered intramuscularly, the vaccines elicited neutralizing and variant (Beta, Gamma, and Delta) cross-neutralizing antibodies against SARS-CoV-2 in all six animals after three vaccinations. The neutralizing response to Omicron was lower with only 4 of 6 animals responding. When delivered at a lower dose by the intradermal route, strong neutralizing antibody responses were only detected in two of six animals. This study confirms that a vaccine previously shown to protect in a hamster model can elicit neutralizing and cross-neutralizing antibodies against SARS-CoV-2 in nonhuman primates. We posit that nCOV-S(JET) has the potential for use as booster vaccine in heterologous vaccination strategies against COVID-19. [ABSTRACT FROM AUTHOR]

The spike (S) glycoprotein of SARS CoV-2 is the target of neutralizing antibodies (NAbs) that are crucial for vaccine effectiveness. The S1 subunit binds ACE2 while the S2 subunit mediates virus-cell membrane fusion. S2 is a class I fusion glycoprotein subunit and contains a central coiled coil that acts as a scaffold for the conformational changes associated with fusion function. The coiled coil of S2 is unusual in that the 3–4 repeat of inward-facing positions are mostly occupied by polar residues that mediate few inter-helical contacts in the prefusion trimer. We examined how insertion of bulkier hydrophobic residues (Val, Leu, Ile, Phe) to fill a cavity next to Ala1016 and Ala1020 in the 3–4 repeat affects the stability and antigenicity of S trimers. Substitution of Ala1016 with bulkier hydrophobic residues in the context of a prefusion-stabilized S trimer, S2P-FHA, was associated with increased thermal stability. S glycoprotein membrane fusion function was retained with Ala1016/Ala1020 cavity-filling mutations associated with improved recombinant S2P-FHA thermostability, however 2 mutants, A1016L and A1016V/A1020I, lacked ability to mediate entry of S-HIV-1 pseudoparticles into 293-ACE2 cells. When assessed as immunogens, two thermostable S2P-FHA mutants derived from the ancestral isolate, A1016L (16L) and A1016V/A1020I (VI) elicited neutralizing antibody with 50%-inhibitory dilutions (ID50s) in the range 2,700–5,110 for ancestral and Delta-derived viruses, and 210–1,744 for Omicron BA.1. The antigens elicited antibody specificities directed to the receptor-binding domain (RBD), N-terminal domain (NTD), fusion peptide and stem region of S2. The VI mutation enabled the production of intrinsically stable Omicron BA.1 and Omicron BA.4/5 S2P-FHA-like ectodomain oligomers in the absence of an external trimerization motif (T4 foldon), thus representing an alternative approach for stabilizing oligomeric S glycoprotein vaccines. Author summary: First-generation SARS CoV-2 vaccines that generate immune responses to ancestral Spike glycoprotein sequences have averted at least 14.4 million deaths, but their effectiveness against the recently emerged Omicron lineages is reduced. The updating of booster vaccines with variant Spike sequences are therefore likely required to maintain population immunity as the pandemic continues to evolve. The Spike is a trimeric integral membrane protein with a membrane spanning sequence at its C-terminus. The Spike protein-based vaccine that is currently licensed for human use is produced by a complex process that reconstitutes the Spike in an adjuvanted nanoparticle. Alternatively, production of the Spike trimer as a soluble protein generally requires replacement of the membrane spanning sequence with a foreign often highly immunogenic trimerization motif that can complicate clinical advancement. We used systematic structure-directed mutagenesis coupled with functional studies to identify an alternative stabilization approach that negates the requirement for an external trimerization motif or membrane-spanning sequence. The replacement of 2 alanine residues that are associated with a cavity in the core of the Spike trimer with bulkier hydrophobic residues resulted in increased Spike thermal stability. Thermostable Spike mutants retained major conserved neutralizing antibody epitopes and the ability to elicit broad neutralizing antibody responses. One such mutation, referred to as VI, enabled the production of intrinsically stable Omicron variant Spike ectodomain oligomers in the absence of an external trimerization motif. The VI mutation potentially enables a simplified method for producing a stable oligomeric S ectodomain glycoprotein vaccine. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has evolved quickly, with different variants of concern resulting in the need to offer continued protection through booster vaccinations. The duration of enhanced protection with booster doses against severe COVID-19 is still unclear. Understanding this is critical to recommendations on the frequency of future booster doses. Methods: Utilising a Hospital Information System for COVID-19 established in Chiang Mai, Thailand, we conducted a cohort study by linking patient-level data of laboratory-confirmed COVID-19 cases to the national immunization records, during the omicron predominant period (1 February– 31 July 2022). Results: Out of 261,103 adults with COVID-19 included in the study, there were 333 (0.13%) severe COVID-19 cases and 190 (0.07%) deaths. Protection against severe COVID-19 was highest with boosters received >14–60 days prior to positive test (93%) and persisted at >60–120 days (91%) but started to wane at >120–180 days (77%) and further at >180 days (68%). The rate of waning differed with age. Those ≥70 years showed faster waning of booster vaccine responses as compared to those aged 18–49 years, who retained good responses up to 180 days. Equivalent risk reduction against severe COVID-19 was seen with all the vaccine types used as boosters in Thailand. Conclusions: Booster doses provided high levels of protection against severe COVID-19 with omicron, up to 4 months. Repeat boosters will be required to continue protection beyond 4 months, particularly in the elderly. mRNA and viral vector vaccines can be used flexibly to improve booster coverage. [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 non-Spike (S) structural protein targets on nucleocapsid (N), membrane (M) and envelope (E), critical in the host cell interferon response and memory T-cell immunity, are grossly overlooked in COVID vaccine development. The current Spike-only vaccines bear an intrinsic shortfall for promotion of a fuller T cell immunity. Vaccines designed to target conserved epitopes could elicit strong cellular immune responses that would synergize with B cell responses and lead to long-term vaccine success. We pursue a universal (pan-SARS-CoV-2) vaccine against Delta, Omicrons and ever-emergent new mutants. Methods and findings: We explored booster immunogenicity of UB-612, a multitope-vaccine that contains S1-RBD-sFc protein and sequence-conserved promiscuous Th and CTL epitope peptides on the Sarbecovirus N, M and S2 proteins. To a subpopulation (N = 1,478) of infection-free participants (aged 18–85 years) involved in a two-dose Phase-2 trial, a UB-612 booster (third dose) was administered 6–8 months after the second dose. The immunogenicity was evaluated at 14 days post-booster with overall safety monitored until the end of study. The booster induced high viral-neutralizing antibodies against live Wuhan WT (VNT50, 1,711) and Delta (VNT50, 1,282); and against pseudovirus WT (pVNT50, 11,167) vs. Omicron BA.1/BA.2/BA.5 variants (pVNT50, 2,314/1,890/854), respectively. The lower primary neutralizing antibodies in the elderly were uplifted upon boosting to approximately the same high level in young adults. UB-612 also induced potent, durable Th1-oriented (IFN-γ+-) responses (peak/pre-boost/post-boost SFU/106 PBMCs, 374/261/444) along with robust presence of cytotoxic CD8+ T cells (peak/pre-boost/post-boost CD107a+-Granzyme B+, 3.6%/1.8%/1.8%). This UB-612 booster vaccination is safe and well tolerated without SAEs. Conclusions: By targeting conserved epitopes on viral S2, M and N proteins, UB-612 could provide potent, broad and long-lasting B-cell and T-cell memory immunity and offers the potential as a universal vaccine to fend off Omicrons and new VoCs without resorting to Omicron-specific immunogens. Trial registration: ClinicalTrials.gov: NCT04773067; ClinicalTrials.gov ID: NCT05293665; ClinicalTrials.gov ID: NCT05541861. Author summary: The Omicron variant of SARS-CoV-2 has swept the globe with a rapid succession of dominating sublineages from BA.1, BA.2, to the current BA.5 with increasing infectivity and antibody evasion. Concerningly, the non-Spike structure proteins that promote T-cell immunity have been grossly overlooked in vaccine development. Looking beyond short-interval boosters and omicron-updated vaccines, a pragmatic approach to curbing ever-emergent new mutants would be "universal (pan-SARS-CoV-2) vaccines" as exemplified by UB-612, a multitope-vaccine armed with Spike (S1-RBD and S2) and non-Spike (Nucleocapsid N and Membrane M) targets, allowing booster vaccination to elicit broadly-recognizing and durable B-/T-cell memory immunity. Sequence-conserved Th/CTL epitope peptides were designed from S2, N and M proteins to synergistically enhance memory helper and cytotoxic T-cell immunity and RBD targeted B-cell immunity. [ABSTRACT FROM AUTHOR]

Rational design of new vaccines against pulmonary tuberculosis is imperative. Early secreted antigens (Esx) G and H are involved in metal uptake, drug resistance, and immune response evasion. These characteristics make it an ideal target for rational vaccine development. The aim of this study is to show the rational design of epitope-based peptide vaccines by using bioinformatics and structural vaccinology tools. A total of 4.15 μs of Molecular Dynamics simulations were carried out to describe the behavior in solution of heterodimer, single epitopes, and epitopes loaded into MHC-II complexes. In order to predict T and B cell epitopes for antigenic activation, bioinformatic tools were used. Hence, we propose three epitopes with the potential to design pulmonary tuberculosis vaccines. The possible use of the proposed epitopes includes subunit vaccines, as a booster in BCG vaccination to improve its immune response, as well as the generation of antibodies that interfere with the Mycobacterium tuberculosis homeostasis, affecting its survival. [ABSTRACT FROM AUTHOR]

Background and aims: Vaccination is the most powerful public health intervention proven to be safe and effective in the battle against the coronavirus disease-2019 (COVID-19) pandemic. Despite the potential therapeutic benefits of primer vaccine dosage regimens, public perceptions of COVID-19 vaccine booster dose (VBD) acceptance and hesitancy vary among various sub-group populations. This study investigates COVID-19 vaccine booster dose acceptance and compares the multi-dimensional potential factors influencing VBD acceptance and hesitancy among university teachers and the student community in Bangladesh. Methods: This web-based cross-sectional study employed an anonymous, validated, and self-administered questionnaire. The questionnaire items were adopted from a theoretical analysis of the recent relevant literature. The questionnaire was deployed in an on-line-enabled format (Google form) and conveniently distributed to 685 teachers and 990 students between 15th June, 2022 and 15th August, 2022 which resulted in the participation of 1250 (505 teachers vs.745 students) total respondents (response rate 73.72% vs. 75.25%) from various universities in Bangladesh. A non-parametric analytical tool (binary logistic regression) was applied to rationalize the study objectives and a Chi-squared test was performed to estimate the booster- hesitant risky group. Results: The pooled COVID-19 vaccine booster dose acceptance rates were 84.6% (95% CI 81.5─87.7) and 67.2% (95% CI 63.8─70.6) for teachers and students in the university academic community, respectively. In employing a binary logistic regression, this study revealed that out of twelve (12)multi-dimensional key predictors, "equal safety", "risk-benefit ratio", and "variant control" had a significant positive association with VBD acceptance in both sets (p = 0.000, p = 0.000, and p = 0.005, respectively). Varied effects were found for several predictors; post-vaccination "side effects" had a significant negative association (p = 0.020) and "community protection" had significant positive association (p = 0.034) with vaccine booster dose acceptance in the teachers community while these variables were insignificant in the students cohort. "Trust" had a highly significant positive association (p = 0.000);"communication" and "academic attainment" had significant positive associations (p = 0.033 and 0.024, respectively) with VBD acceptance in the students cohort, while these predictors were insignificant in the teachers community. Women were more likely to receive a third dose of the vaccine (OR = 1.4 vs. 0.9 between teacher and student model); however, no significant association between gender and booster vaccine acceptance was found in a comparative Chi-squared model. Therefore, statistically, the booster vaccine-hesitant risky group was not found to implicate the massive booster vaccine drive among the university academic community. Conclusions: COVID-19 booster vaccine acceptability among the student cohort was slightly lower than pre-roll-out intent. The teacher community was more inclined to get booster vaccinated. Moreover, differences were found between the multi-dimensional potential factors associated with VBD acceptance among teachers and students in university settings. This study explicitly confirmed positive attitudes toward the safety, health benefits, and variants control of the COVID-19 VBD under any circumstances. Post-vaccination side effect concern was found to be a barrier to administering booster shots and a reason for booster skepticism. Tailored communication and health education interventions need to be adopted to improve the public awareness of booster vaccine consequences, and limit booster skepticism. [ABSTRACT FROM AUTHOR]

Patients with underlying medical conditions are at high risk of developing serious symptoms of the coronavirus disease 2019 than healthy individuals; therefore, it is necessary to evaluate the immune response to vaccination among them to formulate precision and personalized vaccination strategies. However, inconsistent evidence exists regarding whether patients with underlying medical conditions have lower anti-SARS-CoV-2 spike IgG antibody titers. We performed a cross-sectional study enrolling 2762 healthcare workers who received second doses of BNT162b2 vaccination from three medical and research institutes between June and July, 2021. Medical conditions were surveyed by a questionnaire, and spike IgG antibody titers were measured with chemiluminescent enzyme immunoassay using serum collected on the median of 62 days after the second vaccination. Multilevel linear regression model was used to estimate geometric mean and ratio of mean (95% confidence interval, CI) for the presence and absence of medical conditions and treatments. Among all participants (median age, 40 years [interquartile range, 30–50]; male proportion, 29.4%), the prevalence of hypertension, diabetes, chronic lung disease, cardiovascular disease, and cancer was 7.5%, 2.3%, 3.8%, 1.8%, and 1.3%, respectively. Patients with treated hypertension had lower antibody titers than those without hypertension; the multivariable-adjusted ratio of mean (95% CI) was 0.86 (0.76–0.98). Patients with untreated and treated diabetes had lower antibody titers than those without diabetes; the multivariable-adjusted ratio of mean (95% CI) was 0.63 (0.42–0.95) and 0.77 (0.63–0.95), respectively. No substantial difference was observed between the presence or absence of chronic lung disease, cardiovascular disease, or cancer. Patients with untreated hypertension and patients with untreated and treated diabetes had lower spike IgG antibody titers than participants without those medical conditions, suggesting that continuous monitoring of antibody titers and further booster shots could be necessary to maintain adaptive immunity in patients with hypertension or diabetes. [ABSTRACT FROM AUTHOR]