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BackgroundDespite lower circulation of influenza virus throughout 2020-2022 during the COVID-19 pandemic, seasonal influenza vaccination has remained a primary tool to reduce influenza-associated illness and death. The relationship between the decision to receive a COVID-19 vaccine and/or an influenza vaccine is not well understood.MethodsWe assessed predictors of receipt of 2021-2022 influenza vaccine in a secondary analysis of data from a case-control study enrolling individuals who received SARS-CoV-2 testing. We used mixed effects logistic regression to estimate factors associated with receipt of seasonal influenza vaccine. We also constructed multinomial adjusted marginal probability models of being vaccinated for COVID-19 only, seasonal influenza only, or both as compared with receipt of neither vaccination.ResultsAmong 1261 eligible participants recruited between 22 October 2021-22 June 2022, 43% (545) were vaccinated with both seasonal influenza vaccine and >1 dose of a COVID-19 vaccine, 34% (426) received >1 dose of a COVID-19 vaccine only, 4% (49) received seasonal influenza vaccine only, and 19% (241) received neither vaccine. Receipt of >1 COVID-19 vaccine dose was associated with seasonal influenza vaccination (adjusted odds ratio [aOR]: 3.72; 95% confidence interval [CI]: 2.15-6.43); this association was stronger among participants receiving >1 COVID-19 booster dose (aOR = 16.50 [10.10-26.97]). Compared with participants testing negative for SARS- CoV-2 infection, participants testing positive had lower odds of receipt of 2021-2022 seasonal influenza vaccine (aOR = 0.64 [0.50-0.82]).ConclusionsRecipients of a COVID-19 vaccine were more likely to receive seasonal influenza vaccine during the 2021-2022 season. Factors associated with individuals' likelihood of receiving COVID-19 and seasonal influenza vaccines will be important to account for in future studies of vaccine effectiveness against both conditions. Participants who tested positive for SARS-CoV-2 in our sample were less likely to have received seasonal influenza vaccine, suggesting an opportunity to offer influenza vaccination before or after a COVID-19 diagnosis.

BackgroundWe aimed to evaluate the feasibility of implementing an emergency department (ED)-based Coronavirus Disease of 2019 (COVID-19) vaccination protocol in a population of unhoused patients.MethodsOn June 10, 2021, a best practice alert (BPA) was implemented that fired when an ED provider opened the charts of unhoused patients and prompted the provider to order COVID-19 vaccination for eligible patients. We downloaded electronic medical record data of patients who received a COVID-19 vaccine in the ED between June 10, 2021 and August 26, 2021. The outcomes of interest were the number of unhoused, and the total number of patients vaccinated for COVID-19 during the study period. Data were described with simple descriptive statistics.ResultsThere were 25,871 patient encounters in 19,992 unique patients (mean 1.3 visits/patient) in the emergency department during the study period. There were 1,474 (6% of total ED population) visits in 1,085 unique patients who were unhoused (mean 1.4 visits/patient). The BPA fired in 1,046 unhoused patient encounters (71% of PEH encounters) and was accepted in 79 (8%). Forty-three unhoused patients were vaccinated as a result of the BPA (4% of BPA fires) and 18 unhoused patients were vaccinated without BPA prompting. An additional 76 domiciled patients were vaccinated in the ED.ConclusionsImplementing an ED-based COVID-19 vaccination program is feasible, however, only a small number of patients underwent COVID-19 vaccination. Further studies are needed to explore the utility of using the ED as a setting for COVID-19 vaccination.

Willingness to vaccinate and test are critical in the COVID-19 pandemic. We study the effects of two measures to increase the support of vaccination and testing: defaults and monetary compensations. Some organizations, such as restaurants, fire departments, hospitals, or governments in some countries, have used these measures. Yet there is the concern that compensations could erode intrinsic motivation and decrease vaccination intentions. We show that, in the early stages of the pandemic, both approaches, compensations and defaults, significantly increased COVID-19 test demand and vaccine intentions. Compensations for vaccines, however, need to be large enough because low compensations can backfire. We estimate heterogeneous treatment effects to document which groups are more likely to respond to these measures. The results show that defaults and avoidance of small compensations are especially important for individuals who are more skeptical of the vaccine, measured by their trust in the vaccine and their political views. Hence, both measures could be used in a targeted manner to achieve stronger results. This paper was accepted by Yan Chen, behavioral economics and decision analysis. Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2022.4405 .

BackgroundCoronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) studies are increasingly reporting relative VE (rVE) comparing a primary series plus booster doses with a primary series only. Interpretation of rVE differs from traditional studies measuring absolute VE (aVE) of a vaccine regimen against an unvaccinated referent group. We estimated aVE and rVE against COVID-19 hospitalization in primary-series plus first-booster recipients of COVID-19 vaccines.MethodsBooster-eligible immunocompetent adults hospitalized at 21 medical centers in the United States during December 25, 2021-April 4, 2022 were included. In a test-negative design, logistic regression with case status as the outcome and completion of primary vaccine series or primary series plus 1 booster dose as the predictors, adjusted for potential confounders, were used to estimate aVE and rVE.ResultsA total of 2060 patients were analyzed, including 1104 COVID-19 cases and 956 controls. Relative VE against COVID-19 hospitalization in boosted mRNA vaccine recipients versus primary series only was 66% (95% confidence interval [CI], 55%-74%); aVE was 81% (95% CI, 75%-86%) for boosted versus 46% (95% CI, 30%-58%) for primary. For boosted Janssen vaccine recipients versus primary series, rVE was 49% (95% CI, -9% to 76%); aVE was 62% (95% CI, 33%-79%) for boosted versus 36% (95% CI, -4% to 60%) for primary.ConclusionsVaccine booster doses increased protection against COVID-19 hospitalization compared with a primary series. Comparing rVE measures across studies can lead to flawed interpretations of the added value of a new vaccination regimen, whereas difference in aVE, when available, may be a more useful metric.

BackgroundLittle is known about coronavirus disease 2019 (COVID-19) vaccination in Africa. We sought to understand Malawian healthcare workers' (HCWs') COVID-19 vaccination and its hypothesized determinants.MethodsIn March 2021, as the COVID-19 vaccine roll-out commenced in Malawi, we surveyed clinical and lay cadre HCWs (n=400) about their uptake of the vaccine and potential correlates (informed by the WHO Behavioral and Social Drivers of COVID-19 Vaccination framework). We analyzed uptake and used adjusted multivariable logistic regression models to explore how 'what people think and feel' constructs were associated with HCWs' motivation to be vaccinated.ResultsOf the surveyed HCWs, 82.5% had received the first COVID-19 vaccine dose. Motivation (eagerness to be vaccinated) was strongly associated with confidence in vaccine benefits (adjusted OR [aOR] 9.85, 95% CI 5.50 to 17.61) and with vaccine safety (aOR 4.60, 95% CI 2.92 to 7.23), but not with perceived COVID-19 infection risk (aOR 1.38, 95% CI 0.88 to 2.16). Of all the information sources about COVID-19 vaccination, 37.5% were reportedly negative in tone.ConclusionsHCWs in Malawi have a high motivation to be vaccinated and a high COVID-19 vaccine uptake. Disseminating vaccine benefits and safety messages via social media and social networks may be persuasive for individuals who are unmotivated to be vaccinated and less likely to accept the COVID-19 vaccine.

Respiratory syncytial virus (RSV) is a leading cause of upper and lower respiratory tract infection, especially in children and the elderly. Various vaccines containing the major transmembrane surface proteins of RSV (proteins F and G) have been tested; however, they have either afforded inadequate protection or are associated with the risk of vaccine-enhanced disease (VED). Recently, F protein-based maternal immunization and vaccines for elderly patients have shown promising results in phase III clinical trials, however, these vaccines have been administered by injection. Here, we examined the potential of using the ectodomain of small hydrophobic protein (SHe), also an RSV transmembrane surface protein, as a nasal vaccine antigen. A vaccine was formulated using our previously developed cationic cholesteryl-group-bearing pullulan nanogel as the delivery system, and SHe was linked in triplicate to pneumococcal surface protein A as a carrier protein. Nasal immunization of mice and cotton rats induced both SHe-specific serum IgG and mucosal IgA antibodies, preventing viral invasion in both the upper and lower respiratory tracts without inducing VED. Moreover, nasal immunization induced greater protective immunity against RSV in the upper respiratory tract than did systemic immunization, suggesting a critical role for mucosal RSV-specific IgA responses in viral elimination at the airway epithelium. Thus, our nasal vaccine induced effective protection against RSV infection in the airway mucosa and is therefore a promising vaccine candidate for further development.

PurposeGeographic disparities exist in uptake of the human papillomavirus vaccine (HPV). In 2020, the National Immunization Survey-Teen reported that adolescents living in nonmetropolitan statistical areas (MSAs) had lower HPV vaccination coverage (≥ 1 dose) compared to adolescents living in MSA principal cities. This paper describes the implementation and evaluation of a multilevel pilot intervention study to increase uptake of the HPV vaccine among adolescent patients ages 11-17 of a rural health clinic.MethodsThis parent, primary care team, and clinic multilevel pilot intervention was guided by evidence-based approaches to increase HPV vaccinations, formative research, and input from the community. HPV vaccination initiation and completion rates were analyzed at baseline and 23 months follow-up.FindingsThe proportion of adolescent patients ages 11-17 who had initiated the HPV vaccine series was significantly greater at follow-up compared to baseline, (82.7% compared to 52.4%), χ2 (1, n = 498) = 49.2, P < .0001. The proportion of adolescent patients ages 11-17 who had completed the HPV vaccine series was also significantly greater at follow-up compared to baseline, (58.0% compared to 27.0%), χ2 (1, n = 498) = 50.8, P < .0001.ConclusionsThe multilevel intervention significantly increased HPV initiation and completion rates among adolescent patients ages 11-17 at this rural health clinic. This study demonstrates the feasibility of utilizing a multilevel intervention to address low HPV vaccination rates among rural adolescents and the potential of employing this strategy for a large-scale randomizing-controlled trial.

Efficacy of cancer vaccines remains low and mechanistic understanding of antigen presenting cell function in cancer may improve vaccine design and outcomes. Here, we analyze the transcriptomic and immune-metabolic profiles of Dendritic Cells (DCs) from 35 subjects enrolled in a trial of DC vaccines in late-stage melanoma (NCT01622933). Multiple platforms identify metabolism as an important biomarker of DC function and patient overall survival (OS). We demonstrate multiple immune and metabolic gene expression pathway alterations, a functional decrease in OCR/OXPHOS and increase in ECAR/glycolysis in patient vaccines. To dissect molecular mechanisms, we utilize single cell SCENITH functional profiling and show patient clinical outcomes (OS) correlate with DC metabolic profile, and that metabolism is linked to immune phenotype. With single cell metabolic regulome profiling, we show that MCT1 (monocarboxylate transporter-1), a lactate transporter, is increased in patient DCs, as is glucose uptake and lactate secretion. Importantly, pre-vaccination circulating myeloid cells in patients used as precursors for DC vaccine generation are significantly skewed metabolically as are several DC subsets. Together, we demonstrate that the metabolic profile of DC is tightly associated with the immunostimulatory potential of DC vaccines from cancer patients. We link phenotypic and functional metabolic changes to immune signatures that correspond to suppressed DC differentiation.

We assessed the humoral immune responses to a COVID-19 vaccine in a well-controlled rhesus macaque model compared to humans immunized with two mRNA vaccines over several months post-second dose. The plasma IgG levels against seven coronaviruses (including SARS-CoV-2) and antibody subtypes (IgG 1-4 and IgM) against SARS-CoV-2 were evaluated using multiplex assays. The neutralization capacity of plasma antibodies against the original SAR-CoV-2 isolate and nine variants was evaluated in vaccinated humans and non-human primates. Immunization of macaques and humans with SARS-CoV-2 vaccines induced a robust neutralizing antibody response. In non-SIV-infected adult macaques immunized with an adenoviral vector expressing S-RBD (n = 7) or N protein (n = 3), elevated levels of IgG and neutralizing antibodies were detected 2 weeks post-second dose. Immune responses to the S-RBD vaccine in SIV-infected adult macaques (n = 2) were similar to the non-SIV-infected animals. Adult humans immunized with Pfizer (n = 35) or Moderna (n = 18) vaccines developed IgG and neutralizing antibodies at 4 weeks post-second dose. In both vaccine groups, IgG 1 was the predominant subtype, followed by IgG 3. The IgG levels, including total and IgG 1,2,3 elicited by the Moderna vaccine, were significantly higher than the corresponding levels elicited by the Pfizer vaccine at 4 weeks post-second dose. A significant correlation was observed between the plasma total IgG antibody levels and neutralization titers in both macaques and humans. Furthermore, broad-spectrum neutralization antibodies against several variants of SARS-CoV-2 were detected in the plasma of both macaques and humans after two vaccinations.

IntroductionIn the context of recurrent surges of SARS-CoV-2 infections, a detailed characterization of antibody persistence over a 6-month period following vaccine booster dose is necessary to crafting effective public health policies on repeat vaccination.MethodsTo characterize the SARS-CoV-2 antibody profile of a healthcare worker population over a 6-month period following mRNA vaccination and booster dose. 323 healthcare workers at an academic medical center in Orange County, California who had completed primary vaccination and booster dose against SARS-CoV-2 were recruited for the study. A total of 690 blood specimens over a 6-month period were collected via finger-stick blood and analyzed for the presence of antibodies against 9 SARS-CoV-2 antigens using a coronavirus antigen microarray.ResultsThe primary outcome of this study was the average SARS-CoV-2 antibody level as measured using a novel coronavirus antigen microarray. Additional outcomes measured include levels of antibodies specific to SARS-CoV-2 variants including Delta, Omicron BA.1, and BA.2. We also measured SARS-CoV-2 neutralization capacity for a subset of the population to confirm correlation with antibody levels. Although antibodies against SARS-CoV-2 wane throughout the 6-month period following a booster dose, antibody levels remain higher than pre-boost levels. However, a booster dose of vaccine based on the original Wuhan strain generates approximately 3-fold lower antibody reactivity against Omicron variants BA.1 and BA.2 as compared to the vaccine strain. Despite waning antibody levels, neutralization activity against the vaccine strain is maintained throughout the 6-month period.DiscussionIn the context of recurrent surges of SARS-CoV-2 infections, our data indicate that breakthrough infections are likely driven by novel variants with different antibody specificity and not by time since last dose of vaccination, indicating that development of vaccinations specific to these novel variants is necessary to prevent future surges of SARS-CoV-2 infections.

BackgroundCOVID-19 vaccine uptake has been uneven, particularly across racial/ethnic and age groups. This study seeks to understand factors associated with COVID-19 vaccine uptake in a large cross-sectional sample of predominantly Latinos/Latinas individuals living near the US/Mexico border.MethodsData are extracted from a 176-item survey conducted as part of a parent study focused on the co-creation of a COVID-19 testing program for underserved communities developed through a partnership between an academic institution and a Federally Qualified Health Center. The following participant variables were examined: health history, COVID-19 symptoms, COVID-19 testing and vaccine experiences, and perceptions of sources of health information. Participant characteristics were compared using chi-square tests. Multivariate logistic regressions were used for the final statistical model.ResultsFrom 1 May 2021 to 30 April 2022, 4,964 adults, 66% of whom were identified as women, completed the survey. Approximately 80% of participants reported having received at least one COVID-19 vaccine. Female sex, older age, Hispanic/Latino(a) ethnicity, previous influenza vaccination, advanced education, and perceived elevated risk of COVID-19 were significantly (p < 0.05) associated with having received a COVID-19 vaccine. Regarding sources of health information, individuals who indicated they trust their doctor, healthcare provider, or the US government "a great deal" were more likely to have received a COVID-19 vaccine compared to individuals who indicated that they trusted these sources "not at all." In contrast, those who reported having "a great deal" of trust in their faith leader or their social media contacts were significantly less likely to have received a COVID-19 vaccine than those who reported that they trusted these sources "not at all."ConclusionSex, education, past influenza vaccination, perceived risk of COVID-19 infection, and trust in specific sources of information were correlated with the uptake of COVID-19 vaccination. Additional research is needed to better understand why this confluence of factors, particularly the unique findings about trusted sources of information, are associated with vaccine uptake. Understanding these associations, specifically within underserved, Latino/Hispanic communities, is an important first step to inform efforts aimed at increasing and sustaining COVID-19 vaccine uptake and adoption of other public health interventions.

Abstract: Our study utilizes network science to examine how uneven vaccine distribution affects mass vaccination strategies in the United States. Using mobility network data and epidemiological models, we find that distributing a fixed quantity of additional vaccines across Census Block Groups (CBGs) can vary case count reductions by up to 200%. This highlights the impact of vaccination heterogeneity in mobility networks on epidemic outcomes. Our efficient algorithm identifies optimal vaccine distribution for maximum case reduction. Simulations show a possible 9.5% decrease in case numbers with just a 1% increase in the national vaccination rate if vaccines are optimally distributed. This result surpasses those from other vaccine distribution models. Our findings underline the need for policymakers to understand the interaction between vaccination patterns and mobility networks, suggesting that grasping geographical vaccine uptake variations could be as crucial as raising the overall vaccination rate.

BackgroundInequities in COVID-19 vaccine accessibility and reliable COVID-related information disproportionately affected marginalized racial and ethnic communities in the U.S. The Get Out the Vaccine (GOTVax) program, an innovative statewide government-funded COVID-19 vaccine canvassing program in California, aimed to reduce structural barriers to COVID-19 vaccination in high-risk communities with low vaccination rates. GOTVax consisted of a community-academic-government partnership with 34 local trusted community-based organizations' (CBOs) to conduct COVID-19 vaccine outreach, education, and vaccine registration. The purpose of this qualitative evaluation study was to explore the barriers and facilitators of using local CBOs to deploy a geographically, racially, and ethnically diverse state-wide COVID-19 vaccine outreach program.MethodsSemi-structured online interviews were conducted with participating GOTVax CBO leaders from November 2021 to January 2022. Transcripts were analyzed using reflexive thematic analysis.ResultsThirty-one of 34 CBOs participated (91% response rate). Identified themes encompassed both facilitators and barriers to program participation. Key facilitators included leveraging trust through recognized entities; promoting empathetic, tailored outreach; and flexibility of milestone-based CBO funding contracts for rapid program implementation. Barriers included navigating community sociopolitical, geographic, and cultural factors; managing canvassers' safety; desiring metrics for self-evaluation of outreach success; mitigating canvassing technology challenges; and concerns of program infrastructure initially limiting outreach. CBOs problem-solved barriers with academic and government partners.ConclusionsBetween May and December 2021, the GOTVax program reached over 2 million California residents and registered over 60,000 residents for COVID-19 vaccination. Public health campaigns may improve benefits from leveraging the expertise of community-trusted CBOs and universities by providing flexible infrastructure and funding, allowing CBOs to seamlessly tailor outreach most applicable to local minoritized communities.

IntroductionRespiratory syncytial virus (RSV) can cause lower respiratory tract disease in infants and elderly populations. Despite decades of research, there remains no safe and approved RSV vaccine. Previously, we showed that an RSV G glycoprotein subunit vaccine candidate with a single point mutation within the central conserved domain (CCD), i.e. S177Q, considerably improved immunogenicity.MethodsHere, we examine the development of nanoparticle (NP) vaccines having either an RSV G protein CCD with wild-type sequence (NPWT) or an S177Q mutation (NP-S177Q). The NP vaccine immunogens were adjuvanted with monophosphoryl lipid A (MPLA), a TLR4 agonist to improve Th1- type responses. BALB/c mice were primed with 10 μg of NP-WT vaccine, NPS177Q, or vehicle, rested, and then boosted with a high (25 μg) or low (10 μg) dose of the NP-WT or NP-S177Q homologous candidate and subsequently challenged with RSV A2.ResultsThe results showed that mice boosted with NP-S177Q developed superior immunogenicity and neutralizing antibodies compared to NP-WT boosting. IgG from either NP-S177Q or NP-WT vaccinated mice did not interfere with fractalkine (CX3CL1) binding to CX3CR1 and effectively blocked G protein CX3C-CX3CR1 binding. Both NP-WT and NP-S177Q vaccination induced similar neutralizing antibodies to RSV in challenged mice compared to vehicle control. NP-S177Q boosting improved correlates of protection including reduced BAL cell infiltration following RSV challenge. However, the NP vaccine platform will require improvement due to the poor solubility and the unexpectedly weaker Th1-type IgG2a response.DiscussionThe results from this study support further NP-S177Q vaccine candidate development.

Despite the mass availability of COVID-19 vaccines in the United States, many Americans are still reluctant to take a vaccine as an outcome from exposure to misinformation. Additionally, while scholars have paid attention to COVID-19 vaccine hesitancy, the influence of general vaccine hesitancy for important viruses such as the flu has largely been ignored. Using nationally representative data from Pew Research Center's American Trends Panel survey (Wave 79), this study examined the relationship between perceived misinformation exposure, COVID-19 vaccine hesitancy, flu vaccine acceptance, political ideology, and demographic trends. The findings suggest that those who accepted the flu vaccine were less likely to be COVID-19 vaccine-hesitant. In addition, moderation analyses showed that perceived misinformation exposure increases COVID-19 vaccine hesitancy for conservatives and moderates but not for liberals. However, perceived misinformation exposure influences COVID-19 vaccine hesitancy among conservatives only if they are also flu vaccine-hesitant. Perceived misinformation exposure has no role in COVID-19 vaccine hesitancy if individuals (irrespective of political ideology) are regular with their flu vaccine. The results suggest that the effect of misinformation exposure on negative attitudes toward COVID-19 may be associated with generalized vaccine hesitancy (e.g., flu). The practical and theoretical implications are discussed.

The COVID-19 pandemic caused by SARS-CoV-2 sparked intensive research into the development of effective vaccines, 50 of which have been approved thus far, including the novel mRNA-based vaccines developed by Pfizer and Moderna. Although limiting the severity of the disease, the mRNA-based vaccines presented drawbacks, such as the cold chain requirement. Moreover, antibody levels generated by these vaccines decline significantly after 6 months. These vaccines deliver mRNA encoding the full-length spike (S) glycoprotein of SARS-CoV-2, but must be updated as new strains and variants of concern emerge, creating a demand for adjusted formulations and booster campaigns. To overcome these challenges, we have developed COVID-19 vaccine candidates based on the highly conserved SARS CoV-2, 809-826 B-cell peptide epitope (denoted 826) conjugated to cowpea mosaic virus (CPMV) nanoparticles and bacteriophage Qβ virus-like particles, both platforms have exceptional thermal stability and facilitate epitope delivery with inbuilt adjuvant activity. We evaluated two administration methods: subcutaneous injection and an implantable polymeric scaffold. Mice received a prime-boost regimen of 100 μg per dose (2 weeks apart) or a single dose of 200 μg administered as a liquid formulation, or a polymer implant. Antibody titers were evaluated longitudinally over 50 weeks. The vaccine candidates generally elicited an early Th2-biased immune response, which stimulates the production of SARS-CoV-2 neutralizing antibodies, followed by a switch to a Th1-biased response for most formulations. Exceptionally, vaccine candidate 826-CPMV (administered as prime-boost, soluble injection) elicited a balanced Th1/Th2 immune response, which is necessary to prevent pulmonary immunopathology associated with Th2 bias extremes. While the Qβ-based vaccine elicited overall higher antibody titers, the CPMV-induced antibodies had higher avidity. Regardless of the administration route and formulation, our vaccine candidates maintained high antibody titers for more than 50 weeks, confirming a potent and durable immune response against SARS-CoV-2 even after a single dose.

COVID-19 vaccines have dramatically reduced rates of severe infection requiring hospitalization. However, SARS-CoV-2 variants have reduced vaccine effectiveness at preventing any symptomatic infection. This real-world study analyzed binding and neutralizing antibodies generated after complete vaccination and boosting across three vaccine platforms. Binding antibodies decayed most slowly in people under 60 with hybrid immunity. Neutralizing antibodies against Omicron BA.1 were reduced compared to other variants. The anamnestic anti-spike IgG response to the first boost was more pronounced than after the second boost. Monitoring of the effects of SARS-CoV-2 mutations on disease severity and the effectiveness of therapeutics is warranted.

As concerns related to the COVID-19 pandemic continue, it is critical to understand the impact of vaccination type on neutralizing antibody response durability as well as to identify individual difference factors related to decline in neutralization. This was a head-to-head comparison study following 498 healthy, community volunteers who received the BNT162b2 (n = 287), mRNA-1273 (n = 149), and Ad26.COV2.S (n = 62). Participants completed questionnaires and underwent blood draws prior to vaccination, 1 month, and 6 months after the vaccination series, and neutralizing antibody (nAB) titers at 1- and 6-months post vaccination were quantified using a high-throughput pseudovirus assay. Over 6 months of follow-up, nABs declined in recipients of BNT162b2 and mRNA-1273, while nABs in recipients of Ad26.COV2.S showed a significant increase. At the 6-month time point, nABs to Ad26.COV2.S were significantly higher than nABs to BNT162b2 and equivalent to mRNA-1273. Irrespective of follow-up timing, being older was associated with lower nAB for participants who received BNT162b2 and Ad26.COV2.S but not for those who received mRNA-1273. A higher baseline BMI was associated with a lower nAB for Ad26.COV2.S recipients but not for recipients of other vaccines. Women and non-smokers showed higher nAB compared to men and current smokers, respectively. The durability of neutralizing antibody responses differed by vaccine type and several sociodemographic factors that predicted response. These findings may inform booster recommendations in the future.

BackgroundAlthough mRNA vaccines have overall efficacy preventing morbidity/mortality from SARS-CoV-2 infection, immunocompromised persons remain at risk. Antibodies mostly prevent early symptomatic infection, but cellular immunity, particularly the virus-specific CD8+ T cell response, is protective against disease. Defects in T cell responses to vaccination have not been well characterized in immunocompromised hosts; persons with lung transplantation are particularly vulnerable to vaccine failure with severe illness.MethodsComparison groups included persons with lung transplantation and no history of COVID-19 (21 and 19 persons after initial mRNA vaccination and a third booster vaccination respectively), 8 lung transplantation participants recovered from COVID-19, and 22 non-immunocompromised healthy control individuals after initial mRNA vaccination (without history of COVID-19). Anti-spike T cell responses were assayed by stimulating peripheral blood mononuclear cells (PBMCs) with pooled small overlapping peptides spanning the SARS-CoV-2 spike protein, followed by intracellular cytokine staining (ICS) and flow cytometry for release of cytokines in response to stimulation, including negative controls (no peptide stimulation) and positive controls (phorbol myristate acetate [PMA] and ionomycin stimulation). To evaluate for low frequency memory responses, PBMCs were cultured in the presence of the mRNA-1273 vaccine for 14 days before this evaluation.ResultsIonophore stimulation of PBMCs revealed a less inflammatory milieu in terms of interleukin (IL)-2, IL-4, and IL-10 profiling in lung transplantation individuals, reflecting the effect of immunosuppressive treatments. Similar to what we previously reported in healthy vaccinees, spike-specific responses in lung transplantation recipients were undetectable (

Uncertainties about the efficacy of influenza vaccination for populations with heart failure (HF) in preventing cardiovascular outcomes, as well as lack of effective vaccination strategies, may contribute to low vaccine coverage rate (VCR) in China and globally. We assessed the feasibility of a strategy to promote influenza vaccines in patients hospitalized with acute HF in China and to inform the design of a hybrid effectiveness-implementation cluster randomized trial to evaluate this strategy on mortality and hospital re-admission. We conducted a cluster randomized pilot trial involving 11 hospitals in Henan Province in China, with mixed-methods evaluation between December 2020 and April 2021. A process evaluation involved interviews with 51 key informants (patients, health professionals, policy makers). The intervention included education about influenza vaccination and availability of free vaccines administered prior to hospital discharge for HF patients, while usual care included attending community-based points of vaccination (PoV) for screening and vaccination. Implementation outcomes focused on reach, fidelity, adoption, and acceptability. Recruitment rates were assessed for trial feasibility. Effectiveness outcomes were influenza VCR, HF-specific rehospitalizations and mortality at 90 days. A total of 518 HF patients were recruited from 7 intervention and 4 usual care hospitals (mean of 45 participants per hospital per month). VCR was 89.9% (311/346, 86.1-92.8%) in the intervention group and 0.6% (1/172, 0.0-3.7%) in the control group. The process evaluation demonstrated reach to patients with lower socioeconomic and education status. There was good fidelity of the intervention components, with education and PoV set up processes being adapted to local hospital workflow and workforce capacity. Intervention was acceptable and adopted by patients and health professionals. However, outside of a trial setting, concerns were raised around vaccination reimbursement costs, workforce accountability and capacity. The intervention strategy appears feasible and acceptable for improving VCR in HF patients at county-level hospitals in China. Trial registration: This pilot trial is registered with the acronym PANDA II Pilot (Population Assessment of Influenza and Disease Activity) at ChiCTR.org.cn (ChiCTR2000039081).

ObjectivesEfforts to promote COVID-19 vaccine acceptance must consider the critical role of the emergency department (ED) in providing health care to underserved patients. Focusing on patients who lacked primary care, we sought to elicit the perspectives of unvaccinated ED patients regarding COVID-19 vaccination concerns and potential approaches that might increase their vaccine acceptance.MethodsWe conducted this qualitative interview study from August to November 2021 at four urban EDs in San Francisco, California; Seattle, Washington; Durham, North Carolina; and Philadelphia, Pennsylvania. We included ED patients who were ≥18 years old, fluent in English or Spanish, had not received a COVID-19 vaccine, and did not have primary care physicians or clinics. We excluded patients who were unable to complete an interview, in police custody, under suspicion of active COVID-19 illness, or presented with a psychiatric chief complaint. We enrolled until we reached thematic saturation in relevant domains. We analyzed interview transcripts with a content analysis approach focused on identifying concerns about COVID-19 vaccines and ideas regarding the promotion of vaccine acceptance and potential trusted messengers.ResultsOf 65 patients enrolled, 28 (43%) identified as female, their median age was 36 years (interquartile range 29-49), and 12 (18%) interviews were conducted in Spanish. Primary concerns about COVID-19 vaccines included risk of complications, known and unknown side effects, and fear of contracting COVID-19 from vaccines. Trust played a major role for patients in deciding which sources to use for vaccine information and in engendering vaccine acceptance. Health care providers and family or friends were commonly cited as trusted messengers of information.ConclusionsWe characterized concerns about COVID-19 vaccines, uncovered themes that may promote vaccine acceptance, and identified trusted messengers-primarily health care professionals. These data may inform the development of nuanced COVID-19 vaccine messaging platforms to address COVID-19 vaccine hesitancy among underserved ED populations.

Populations at high risk for COVID-19- including Spanish speakers-may face additional barriers to obtaining COVID-19 vaccinations; by understanding their challenges, we can create more equitable vaccine interventions. In this study, we used interviews to identify barriers and enablers to COVID-19 vaccine uptake among participants in the San Francisco Department of Public Health contact tracing program. Data analysis employed Capability, Opportunity, Motivation Behavior model (COM-B) and the Behavior Change Wheel framework as guides to target barriers with interventions and supporting policies. This paper presents data from interviews focused on COVID-19 vaccine uptake that was part of a project to improve COVID-19 preventive behaviors in San Francisco. We completed seventeen interviews between February and May 2021; six (35%) were completed in English and 11 (65%) in Spanish. Barriers to vaccine uptake included an unprepared health system, fear of side effects, limited knowledge, and conflicting information. Behavioral factors influencing vaccine uptake were mainly related to physical opportunity, automatic motivation, and psychological capability. Interventions that could address the most significant number of barriers included education, enablement, and environmental restructuring. Finally, communication and marketing policies that use diverse multi-lingual social media and environmental planning that includes accessible vaccine sites for people with disabilities, literacy barriers, and limited English proficiency could significantly increase vaccination. Public health departments should tailor interventions to high-risk populations by understanding the specific barriers they face. This exploratory study suggests how implementation science can provide frameworks to achieve this.

IntroductionAs of July 2022, a little over one-third of Guatemalans were fully vaccinated. While COVID-19 vaccination rates are not officially reported nationally by racial/ethnic groups, non-governmental organisations and reporters have observed that COVID-19 vaccination rates are especially low among high-risk Indigenous populations. We conducted one of the first studies on COVID-19 vaccine acceptance in Indigenous populations in the Central Highlands of Guatemala, which aimed to better understand the barriers to COVID-19 vaccine uptake and how to improve vaccine promotional campaigns.MethodsIn November 2021, we conducted eight focus group discussions (FGDs) with 42 Indigenous men and women and 16 in-depth interviews (IDIs) with community health workers, nurses and physicians in Chimaltenango and Sololá. Using a participatory design approach, our qualitative analysis used constant comparative methods to understand the inductive and deductive themes from the FGD and IDI transcripts.ResultsWe found three major overarching barriers to vaccination within the sampled population: (1) a lack of available easily understandable, linguistically appropriate and culturally sensitive COVID-19 vaccine information; (2) vaccine access and supply issues that prevented people from being vaccinated efficiently and quickly; and (3) widespread misinformation and disinformation that prey on people's fears of the unknown and mistrust of the medical establishment and government.ConclusionWhen developing COVID-19 vaccine messages, content should be culturally relevant, appropriate for low-literacy populations and in the languages that people prefer to speak. Promotional materials should be in multiple modalities (print, radio and social media) and also have specific Maya cultural references (dress, food and concepts of disease) to ensure messaging connects with intended targets. This study supports the need for more robust research into best practices for communicating about COVID-19 vaccines to marginalised communities globally and suggests that policy makers should invest in targeted local solutions to increase vaccine uptake.

ObjectivesThe objective of this prospective study was to investigate the role of adaptive immunity in response to SARS-CoV-2 vaccines.Design and methodsA cohort of 677 vaccinated individuals participated in a comprehensive survey of their vaccination status and associated side effects, and donated blood to evaluate their adaptive immune responses by neutralizing antibody (NAb) and T cell responses. The cohort then completed a follow-up survey to investigate the occurrence of breakthrough infections.ResultsNAb levels were the highest in participants vaccinated with Moderna, followed by Pfizer and Johnson & Johnson. NAb levels decreased with time after vaccination with Pfizer and Johnson & Johnson. T cell responses showed no significant difference among the different vaccines and remained stable up to 10 months after the study period for all vaccine types. In multivariate analyses, NAb responses (

The COVID-19 Vaccines Global Access (COVAX) is a World Health Organization (WHO) initiative that aims for an equitable access of COVID-19 vaccines. Despite potential heterogeneous infection levels across a country, countries receiving allotments of vaccines may follow WHO's allocation guidelines and distribute vaccines based on a jurisdictions' relative population size. Utilizing economic-epidemiological modeling, we benchmark the performance of this pro rata allocation rule by comparing it to an optimal one that minimizes the economic damages and expenditures over time, including a penalty representing the social costs of deviating from the pro rata strategy. The pro rata rule performs better when the duration of naturally- and vaccine-acquired immunity is short, when there is population mixing, when the supply of vaccine is high, and when there is minimal heterogeneity in demographics. Despite behavioral and epidemiological uncertainty diminishing the performance of the optimal allocation, it generally outperforms the pro rata vaccine distribution rule.

We examined parents' COVID-19 vaccination intentions for their children, reasons for not vaccinating, and the potential impact of a school/daycare vaccination requirement or pediatrician's recommendation on vaccination intentions. Two online surveys were conducted in June-July and September-October 2021, before pediatric COVID-19 vaccines were authorized for emergency use in children age

IntroductionWhile antibodies raised by SARS-CoV-2 mRNA vaccines have had compromised efficacy to prevent breakthrough infections due to both limited durability and spike sequence variation, the vaccines have remained highly protective against severe illness. This protection is mediated through cellular immunity, particularly CD8+ T cells, and lasts at least a few months. Although several studies have documented rapidly waning levels of vaccine-elicited antibodies, the kinetics of T cell responses have not been well defined.MethodsInterferon (IFN)-γ enzyme-linked immunosorbent spot (ELISpot) assay and intracellular cytokine staining (ICS) were utilized to assess cellular immune responses (in isolated CD8+ T cells or whole peripheral blood mononuclear cells, PBMCs) to pooled peptides spanning spike. ELISA was performed to quantitate serum antibodies against the spike receptor binding domain (RBD).ResultsIn two persons receiving primary vaccination, tightly serially evaluated frequencies of anti-spike CD8+ T cells using ELISpot assays revealed strikingly short-lived responses, peaking after about 10 days and becoming undetectable by about 20 days after each dose. This pattern was also observed in cross-sectional analyses of persons after the first and second doses during primary vaccination with mRNA vaccines. In contrast, cross-sectional analysis of COVID-19-recovered persons using the same assay showed persisting responses in most persons through 45 days after symptom onset. Cross-sectional analysis using IFN-γ ICS of PBMCs from persons 13 to 235 days after mRNA vaccination also demonstrated undetectable CD8+ T cells against spike soon after vaccination, and extended the observation to include CD4+ T cells. However, ICS analyses of the same PBMCs after culturing with the mRNA-1273 vaccine in vitro showed CD4+ and CD8+ T cell responses that were readily detectable in most persons out to 235 days after vaccination.DiscussionOverall, we find that detection of spike-targeted responses from mRNA vaccines using typical IFN-γ assays is remarkably transient, which may be a function of the mRNA vaccine platform and an intrinsic property of the spike protein as an immune target. However, robust memory, as demonstrated by capacity for rapid expansion of T cells responding to spike, is maintained at least several months after vaccination. This is consistent with the clinical observation of vaccine protection from severe illness lasting months. The level of such memory responsiveness required for clinical protection remains to be defined.

BackgroundSocial media has emerged as a critical mass communication tool, with both health information and misinformation now spread widely on the web. Prior to the COVID-19 pandemic, some public figures promulgated anti-vaccine attitudes, which spread widely on social media platforms. Although anti-vaccine sentiment has pervaded social media throughout the COVID-19 pandemic, it is unclear to what extent interest in public figures is generating anti-vaccine discourse.ObjectiveWe examined Twitter messages that included anti-vaccination hashtags and mentions of public figures to assess the connection between interest in these individuals and the possible spread of anti-vaccine messages.MethodsWe used a data set of COVID-19-related Twitter posts collected from the public streaming application programming interface from March to October 2020 and filtered it for anti-vaccination hashtags "antivaxxing," "antivaxx," "antivaxxers," "antivax," "anti-vaxxer," "discredit," "undermine," "confidence," and "immune." Next, we applied the Biterm Topic model (BTM) to output topic clusters associated with the entire corpus. Topic clusters were manually screened by examining the top 10 posts most highly correlated in each of the 20 clusters, from which we identified 5 clusters most relevant to public figures and vaccination attitudes. We extracted all messages from these clusters and conducted inductive content analysis to characterize the discourse.ResultsOur keyword search yielded 118,971 Twitter posts after duplicates were removed, and subsequently, we applied BTM to parse these data into 20 clusters. After removing retweets, we manually screened the top 10 tweets associated with each cluster (200 messages) to identify clusters associated with public figures. Extraction of these clusters yielded 768 posts for inductive analysis. Most messages were either pro-vaccination (n=329, 43%) or neutral about vaccination (n=425, 55%), with only 2% (14/768) including anti-vaccination messages. Three main themes emerged: (1) anti-vaccination accusation, in which the message accused the public figure of holding anti-vaccination beliefs; (2) using "anti-vax" as an epithet; and (3) stating or implying the negative public health impact of anti-vaccination discourse.ConclusionsMost discussions surrounding public figures in common hashtags labelled as "anti-vax" did not reflect anti-vaccination beliefs. We observed that public figures with known anti-vaccination beliefs face scorn and ridicule on Twitter. Accusing public figures of anti-vaccination attitudes is a means of insulting and discrediting the public figure rather than discrediting vaccines. The majority of posts in our sample condemned public figures expressing anti-vax beliefs by undermining their influence, insulting them, or expressing concerns over public health ramifications. This points to a complex information ecosystem, where anti-vax sentiment may not reside in common anti-vax-related keywords or hashtags, necessitating further assessment of the influence that public figures have on this discourse.

Background and purposeRecent new mutations and increases in transmission of COVID-19 among adolescents and children highlight the importance of identifying which factors influence parental decisions regarding vaccinating their children. The current study aims to explore whether child vulnerability and parents' attitudes toward vaccines mediate the association between perceived financial well-being and vaccine hesitancy among parents.MethodA predictive, cross-sectional, multi-country online questionnaire was administered with a convenience sample of 6,073 parents (Australia, 2,734; Iran, 2,447; China, 523; Turkey, 369). Participants completed the Parent Attitude About Child Vaccines (PACV), the Child Vulnerability Scale (CVS), a Financial Well-being (FWB) measure, and Parental Vaccine Hesitancy (PVH) questionnaire.ResultsThe current study revealed that perceived financial well-being had significant and negative associations with parents' attitudes toward COVID-19 vaccines and child vulnerability among the Australian sample. Contrary to the Australian findings, results from Chinese participants indicated that financial well-being had significant and positive predictive effects on parent attitudes toward vaccines, child vulnerability, and parental vaccine hesitancy. The results of the Iranian sample revealed that parents' attitudes toward vaccines and child vulnerability significantly and negatively predicted parental vaccine hesitancy.ConclusionThe current study revealed that a parents' perceived financial well-being had a significant and negative relationship with parental attitudes about vaccines and child vulnerability; however, it did not significantly predict parental vaccine hesitancy among Turkish parents as it did for parents in Australia, Iran, and China. Findings of the study have policy implications for how certain countries may tailor their vaccine-related health messages to parents with low financial wellbeing and parents with vulnerable children.

Single dose slow-release vaccines herald a new era in vaccine administration. An ideal device for slow-release vaccine delivery would be minimally invasive and self-administered, making these approaches an attractive alternative for mass vaccination programs, particularly during the time of a pandemic. In this review article, we discuss the latest advances in this field, specifically for prophylactic vaccines able to prevent infectious diseases. Recent studies have found that slow-release vaccines elicit better immune responses and often do not require cold chain transportation and storage, thus drastically reducing the cost, streamlining distribution, and improving efficacy. This promise has attracted significant attention, especially when poor patient compliance of the standard multidose vaccine regimes is considered. Single dose slow-release vaccines are the next generation of vaccine tools that could overcome most of the shortcomings of present vaccination programs and be the next platform technology to combat future pandemics. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants Biology-Inspired Nanomaterials > Protein and Virus-Based Structures.

BackgroundMen who have sex with men (MSM) have suboptimal uptake of human papillomavirus (HPV) and meningococcal vaccines. This study examines barriers and facilitators to HPV and meningococcal vaccination among MSM in a large, racially/ethnically diverse, and medically underserved U.S. region.MethodsIn 2020, we conducted five focus groups with MSM living in the Inland Empire, California. Participants discussed (1) their knowledge about and attitudes toward HPV, meningococcal disease, and related vaccines; and (2) factors that would encourage or discourage vaccine uptake. Data were systematically analyzed to identify salient barriers and facilitators to vaccination.ResultsParticipants (N = 25) had a median age of 29. Most were Hispanic (68%), self-identified as gay (84%), and had college degrees (64%). Key barriers to vaccination included: (1) limited awareness and knowledge about HPV and meningococcal disease, (2) reliance on mainstream healthcare providers for vaccine information, (3) stigma and reluctance to disclose sexual orientation, (4) uncertainty about health insurance coverage and vaccine costs, and (5) distance and time required to access vaccines. Key facilitators to vaccination were: (1) vaccine confidence, (2) perceived severity of HPV and meningococcal disease, (3) bundling vaccination into routine healthcare, and (4) pharmacies as vaccination sites.ConclusionsFindings highlight opportunities for HPV and meningococcal vaccine promotion, including targeted education and awareness campaigns for MSM, LGBT inclusivity training for healthcare providers, and structural interventions to improve vaccine accessibility.

The authors estimate the associations between community socioeconomic composition and changes in coronavirus disease 2019 (COVID-19) vaccination levels in eight large cities at three time points. In March, communities with high socioeconomic status (SES) had significantly higher vaccination rates than low-SES communities. Between March and April, low-SES communities had significantly lower changes in percentage vaccinated than high-SES communities. Between April and May, this difference was not significant. Thus, the large vaccination gap between communities during restricted vaccine eligibility did not narrow when eligibility opened up. The link between COVID-19 vaccination and community disadvantage may lead to a bifurcated recovery whereby advantaged communities move on from the pandemic more quickly while disadvantaged communities continue to suffer.

Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen. The number of chlamydial infections continuous to increase and there is an urgent need for a safe and efficacious vaccine. To assess the ability of the Chlamydia muridarum polymorphic membrane protein G (PmpG) and the plasmid glycoprotein 3 (Pgp3) as single antigens, and in combination with the major outer-membrane protein (MOMP) to induce protection, BALB/c mice were immunized utilizing CpG-1826 and Montanide ISA 720 VG as adjuvants. Following vaccination with MOMP, significant humoral and cell-mediated immune responses were observed, while immunization with PmpG, or Pgp3, elicited weaker immune responses. Weaker immune responses were induced with MOMP+Pgp3 compared with MOMP alone. Following the intranasal challenge with C. muridarum, mice vaccinated with MOMP showed robust protection against body-weight loss, inflammatory responses in the lungs and number of Chlamydia recovered from the lungs. PmpG and Pgp3 elicited weaker protective responses. Mice immunized with MOMP+PmpG, were no better protected than animals vaccinated with MOMP only, while Pgp3 antagonized the protection elicited by MOMP. In conclusion, PmpG and Pgp3 elicited limited protective immune responses in mice against a respiratory challenge with C. muridarum and failed to enhance the protection induced by MOMP alone. The virulence of Pgp3 may result from its antagonistic effect on the immune protection induced by MOMP.

Engineered outer membrane vesicles (OMVs) derived from Gram-negative bacteria are a promising technology for the creation of non-infectious, nanoparticle vaccines against diverse pathogens. However, antigen display on OMVs can be difficult to control and highly variable due to bottlenecks in protein expression and localization to the outer membrane of the host cell, especially for bulky and/or complex antigens. Here, we describe a universal approach for avidin-based vaccine antigen crosslinking (AvidVax) whereby biotinylated antigens are linked to the exterior of OMVs whose surfaces are remodeled with multiple copies of a synthetic antigen-binding protein (SNAP) comprised of an outer membrane scaffold protein fused to a biotin-binding protein. We show that SNAP-OMVs can be readily decorated with a molecularly diverse array of biotinylated subunit antigens, including globular and membrane proteins, glycans and glycoconjugates, haptens, lipids, and short peptides. When the resulting OMV formulations are injected in mice, strong antigen-specific antibody responses are observed that depend on the physical coupling between the antigen and SNAP-OMV delivery vehicle. Overall, these results demonstrate AvidVax as a modular platform that enables rapid and simplified assembly of antigen-studded OMVs for application as vaccines against pathogenic threats.

In 2018, nine-valent human papillomavirus (HPV) vaccine eligibility expanded to include adults aged 27 to 45. This study aimed to identify knowledge, attitudes, and beliefs (KABs) about HPV and HPV vaccination among newly eligible mid-adult men, for whom uptake in adolescence and younger adulthood remains suboptimal. We conducted six virtual focus groups (N = 34 participants) with unvaccinated men aged 27 to 45 living in Southern California's Inland Empire. Data were systematically analyzed to identify emergent themes using the rigorous and accelerated data reduction technique. The sample of men was diverse (79% Hispanic, non-Hispanic Black, Asian, or mixed race/ethnicity; 26% gay or bisexual) and captured participants from across the socioeconomic spectrum. Eighty-eight percent of participants had never received a provider recommendation to be vaccinated against HPV. Many had unanswered questions about HPV and HPV vaccination, could not recall any HPV-related cancers that affect men, and were unaware of their current eligibility for vaccination. Embarrassment and stigma surrounding vaccination against a sexually transmitted infection, concerns about vaccine side effects and safety, and preferences for preventing HPV via "safer sex" and monogamy were salient barriers to vaccination. Nevertheless, many men were eager to learn more about HPV vaccination and engage with health care providers around that topic. Interventions aimed at improving men's knowledge, changing social norms, and supporting health providers to identify HPV vaccine-eligible patients may be especially fruitful for facilitating shared clinical decision-making between mid-adult men and their health care providers.

BackgroundThis United States-based study compared 2 candidate vaccines: RSV/ΔNS2/Δ1313/I1314L, attenuated by NS2 gene-deletion and temperature-sensitivity mutation in the polymerase gene; and RSV/276, attenuated by M2-2 deletion.MethodsRSV-seronegative children aged 6-24 months received RSV/ΔNS2/Δ1313/I1314L (106 plaque-forming units [PFU]), RSV/276 (105 PFU), or placebo intranasally. Participants were monitored for vaccine shedding, reactogenicity, and RSV serum antibodies, and followed over the subsequent RSV season.ResultsEnrollment occurred September 2017 to October 2019. During 28 days postinoculation, upper respiratory illness and/or fever occurred in 64% of RSV/ΔNS2/Δ1313/I1314L, 84% of RSV/276, and 58% of placebo recipients. Symptoms were generally mild. Cough was more common in RSV/276 recipients than RSV/ΔNS2/Δ1313/I1314L (48% vs 12%; P = .012) or placebo recipients (17%; P = .084). There were no lower respiratory illness or serious adverse events. Eighty-eight and 96% of RSV/ΔNS2/Δ1313/I1314L and RSV/276 recipients were infected with vaccine (shed vaccine and/or had ≥4-fold rises in RSV antibodies). Serum RSV-neutralizing titers and anti-RSV F IgG titers increased ≥4-fold in 60% and 92% of RSV/ΔNS2/Δ1313/I1314L and RSV/276 vaccinees, respectively. Exposure to community RSV during the subsequent winter was associated with strong anamnestic RSV-antibody responses.ConclusionsBoth vaccines had excellent infectivity and were well tolerated. RSV/276 induced an excess of mild cough. Both vaccines were immunogenic and primed for strong anamnestic responses.Clinical trials registrationNCT03227029 and NCT03422237.

BackgroundDespite the availability of effective vaccines against COVID-19, booster vaccinations are needed to maintain vaccine-induced protection against variant strains and breakthrough infections. This study aimed to investigate the efficacy, safety, and immunogenicity of the Ad26.COV2.S vaccine (Janssen) as primary vaccination plus a booster dose.MethodsENSEMBLE2 is a randomised, double-blind, placebo-controlled, phase 3 trial including crossover vaccination after emergency authorisation of COVID-19 vaccines. Adults aged at least 18 years without previous COVID-19 vaccination at public and private medical practices and hospitals in Belgium, Brazil, Colombia, France, Germany, the Philippines, South Africa, Spain, the UK, and the USA were randomly assigned 1:1 via a computer algorithm to receive intramuscularly administered Ad26.COV2.S as a primary dose plus a booster dose at 2 months or two placebo injections 2 months apart. The primary endpoint was vaccine efficacy against the first occurrence of molecularly confirmed moderate to severe-critical COVID-19 with onset at least 14 days after booster vaccination, which was assessed in participants who received two doses of vaccine or placebo, were negative for SARS-CoV-2 by PCR at baseline and on serology at baseline and day 71, had no major protocol deviations, and were at risk of COVID-19 (ie, had no PCR-positive result or discontinued the study before day 71). Safety was assessed in all participants; reactogenicity, in terms of solicited local and systemic adverse events, was assessed as a secondary endpoint in a safety subset (approximately 6000 randomly selected participants). The trial is registered with ClinicalTrials.gov, NCT04614948, and is ongoing.FindingsEnrolment began on Nov 16, 2020, and the primary analysis data cutoff was June 25, 2021. From 34 571 participants screened, the double-blind phase enrolled 31 300 participants, 14 492 of whom received two doses (7484 in the Ad26.COV2.S group and 7008 in the placebo group) and 11 639 of whom were eligible for inclusion in the assessment of the primary endpoint (6024 in the Ad26.COV2.S group and 5615 in the placebo group). The median (IQR) follow-up post-booster vaccination was 36·0 (15·0-62·0) days. Vaccine efficacy was 75·2% (adjusted 95% CI 54·6-87·3) against moderate to severe-critical COVID-19 (14 cases in the Ad26.COV2.S group and 52 cases in the placebo group). Most cases were due to the variants alpha (B.1.1.7) and mu (B.1.621); endpoints for the primary analysis accrued from Nov 16, 2020, to June 25, 2021, before the global dominance of delta (B.1.617.2) or omicron (B.1.1.529). The booster vaccine exhibited an acceptable safety profile. The overall frequencies of solicited local and systemic adverse events (evaluated in the safety subset, n=6067) were higher among vaccine recipients than placebo recipients after the primary and booster doses. The frequency of solicited adverse events in the Ad26.COV2.S group were similar following the primary and booster vaccinations (local adverse events, 1676 [55·6%] of 3015 vs 896 [57·5%] of 1559, respectively; systemic adverse events, 1764 [58·5%] of 3015 vs 821 [52·7%] of 1559, respectively). Solicited adverse events were transient and mostly grade 1-2 in severity.InterpretationA homologous Ad26.COV2.S booster administered 2 months after primary single-dose vaccination in adults had an acceptable safety profile and was efficacious against moderate to severe-critical COVID-19. Studies assessing efficacy against newer variants and with longer follow-up are needed.FundingJanssen Research & Development.

ObjectivesWe examined COVID-19 vaccination status, intention, and hesitancy and the effects of five strategies to increase the willingness of unvaccinated adults (≥18 years) to get a COVID vaccine.MethodsOnline surveys were conducted between October 1-17, 2020 (N = 14,946), December 4-16, 2020 (N = 15,229), April 8-22, 2021 (N = 14,557), June 17-July 6, 2021 (N = 30,857), and September 3-October 4, 2021 (N = 33,088) with an internet-based, non-probability opt-in sample of U.S. adults matching demographic quotas. Respondents were asked about current COVID-19 vaccination status, intention and hesitancy to get vaccinated, and reasons for vaccine hesitancy. Unvaccinated respondents were assigned to treatment groups to test the effect of five strategies (endorsements, changing social restrictions, financial incentives, vaccine requirements for certain activities, and vaccine requirements for work). Chi-square tests of independence were performed to detect differences in the response distributions.ResultsWillingness to be vaccinated (defined as being vaccinated or planning to be) increased over time from 47.6 % in October 2020 to 81.1 % in October 2021. By October 2021, across most demographic groups, over 75 % of survey respondents had been or planned to be vaccinated. In terms of strategies: (1) endorsements had no positive effect, (2) relaxing the need for masks and social distancing increased Intention to Get Vaccinated (IGV) by 6.4 % (p

BackgroundSignificant disparities in COVID-19 morbidity and mortality exist for Native American (NA) people, the majority of whom live in urban areas. COVID-19 vaccination is a key strategy for mitigating these disparities; however, vaccination disparities affect NA communities. The current study investigated COVID-19 vaccine decision-making before widespread vaccine rollout occurred, among urban NA communities. We aimed to understand vaccine decision-making factors to develop recommendations about COVID-19 vaccine outreach.MethodsWe conducted three in-depth virtual focus groups with 17 NA adults living in an urban community (Los Angeles County) between December 2020 and January 2021. Participants were recruited through NA community-based organizations and community stakeholders. Reflexive thematic analysis was conducted using Atlas.ti.FindingsParticipants in this study identified two overarching themes with implications for health vaccination campaigns. First, participants described a need for tailored information and outreach, including NA vaccine outreach that addresses misconceptions about vaccine development to calm fears of experimentation and support communication of vaccine evidence specific to NA people. Second, participants suggested strategies to improve public health resources in the urban NA community, such as the need for unified, proactive communication across trusted NA entities, navigation support to improve vaccine accessibility, and adequately resourcing health partnerships with and among trusted NA community agencies for improved reach.ConclusionIn this qualitative study, we found that urban NA participants reported several factors that affected their vaccine decision-making, including a lack of tailored information for their communities. Our findings also underscore the need to work with tribes, tribal leadership, and urban NA serving organizations to coordinate vaccine communication and distribution to urban communities where the majority of NAs now reside. Further, these findings have implications for COVID-19 vaccine outreach among urban NA communities and demonstrate the need for clear and tailored engagement about the COVID-19 vaccine.

IntroductionVaccine hesitancy is still rampant in the United States, including health care personnel. Vaccination of frontline essential workers (e.g. health care workers) is very important, especially during a pandemic. We tested the efficacy of a 4-week online, peer-led intervention (Harnessing Online Peer Education) to promote requests for COVID-19 vaccine information among essential workers.MethodsParticipants (N = 120) and peer leaders (N = 12) were recruited through online advertisements from July 23 to August 20, 2021. Eligibility criteria included: 18 years or older, U.S. resident, English speaker, part of phase 1a or 1 b of COVID-19 vaccine rollout (e.g. frontline essential workers), hadn't received a COVID-19 vaccine but able to receive one. This was a parallel assignment randomised trial. STATA was used to create a randomisation using a random number generator so that all possible assignments of participants and peer leaders to groups were equally likely. Participants were randomly assigned to intervention or control arms that consisted of two private, hidden Facebook groups, each with 30 participants. Peer leaders were randomly assigned to an intervention group, each with six peer leaders. Participants in the intervention arm were randomly assigned to three peer leaders. Participants were blinded after assignment. Peer leaders were tasked with reaching out to their assigned participants at least three times each week. Participants completed a baseline and a post intervention survey. The study is registered on ClinicalTrials.org under identifier NCT04376515 and is no longer recruiting. This work was supported by the NIAID under grant 5R01AI132030-05.ResultsA total of 101 participants analysed (50 intervention and 51 control). Six people in the intervention group and 0 people in the control group requested vaccine information. Ten people in the intervention group and six people in the control group provided proof of vaccination. The odds of requesting vaccine information in the intervention group was 13 times that in the control group (95% confidence interval: (1.5, 1772), p-value = 0.015). Thirty-seven participants in the intervention group and 31 in the control group were engaged at some point during the study.ConclusionsResults suggest peer-led online community groups may help to disseminate health information, aid public health efforts, and combat vaccine hesitancy. Key MessagesThe odds of requesting vaccine information was 13 times in the intervention group.Peer-led online communities may help to disseminate information and aid public health efforts to combat vaccine hesitancy.

ObjectiveReports of efficacy, effectiveness and harms of COVID-19 vaccines have not used key indicators from evidence-based medicine (EBM) that can inform policies about vaccine distribution. This study aims to clarify EBM indicators that consider baseline risks when assessing vaccines' benefits versus harms: absolute risk reduction (ARR) and number needed to be vaccinated (NNV), versus absolute risk of the intervention (ARI) and number needed to harm (NNH).MethodsWe used a multimethod approach, including a scoping review of the literature; calculation of risk reductions and harms from data concerning five major vaccines; analysis of risk reductions in population subgroups with varying baseline risks; and comparisons with prior vaccines.FindingsThe scoping review showed few reports regarding ARR, NNV, ARI and NNH; comparisons of benefits versus harms using these EBM methods; or analyses of varying baseline risks. Calculated ARRs for symptomatic infection and hospitalisation were approximately 1% and 0.1%, respectively, as compared with relative risk reduction of 50%-95% and 58%-100%. NNV to prevent one symptomatic infection and one hospitalisation was in the range of 80-500 and 500-4000. Based on available data, ARI and NNH as measures of harm were difficult to calculate, and the balance between benefits and harms using EBM measures remained uncertain. The effectiveness of COVID-19 vaccines as measured by ARR and NNV was substantially higher in population subgroups with high versus low baseline risks.ConclusionsPriorities for vaccine distribution should target subpopulations with higher baseline risks. Similar analyses using ARR/NNV and ARI/NNH would strengthen evaluations of vaccines' benefits versus harms. An EBM perspective on vaccine distribution that emphasises baseline risks becomes especially important as the world's population continues to face major barriers to vaccine access-sometimes termed 'vaccine apartheid'.

Monovalent COVID-19 mRNA vaccines, designed against the ancestral strain of SARS-CoV-2, successfully reduced COVID-19-related morbidity and mortality in the United States and globally (1,2). However, vaccine effectiveness (VE) against COVID-19-associated hospitalization has declined over time, likely related to a combination of factors, including waning immunity and, with the emergence of the Omicron variant and its sublineages, immune evasion (3). To address these factors, on September 1, 2022, the Advisory Committee on Immunization Practices recommended a bivalent COVID-19 mRNA booster (bivalent booster) dose, developed against the spike protein from ancestral SARS-CoV-2 and Omicron BA.4/BA.5 sublineages, for persons who had completed at least a primary COVID-19 vaccination series (with or without monovalent booster doses) ≥2 months earlier (4). Data on the effectiveness of a bivalent booster dose against COVID-19 hospitalization in the United States are lacking, including among older adults, who are at highest risk for severe COVID-19-associated illness. During September 8-November 30, 2022, the Investigating Respiratory Viruses in the Acutely Ill (IVY) Network§ assessed effectiveness of a bivalent booster dose received after ≥2 doses of monovalent mRNA vaccine against COVID-19-associated hospitalization among immunocompetent adults aged ≥65 years. When compared with unvaccinated persons, VE of a bivalent booster dose received ≥7 days before illness onset (median = 29 days) against COVID-19-associated hospitalization was 84%. Compared with persons who received ≥2 monovalent-only mRNA vaccine doses, relative VE of a bivalent booster dose was 73%. These early findings show that a bivalent booster dose provided strong protection against COVID-19-associated hospitalization in older adults and additional protection among persons with previous monovalent-only mRNA vaccination. All eligible persons, especially adults aged ≥65 years, should receive a bivalent booster dose to maximize protection against COVID-19 hospitalization this winter season. Additional strategies to prevent respiratory illness, such as masking in indoor public spaces, should also be considered, especially in areas where COVID-19 community levels are high (4,5).

BackgroundEfforts to protect residents in nursing homes involve non-pharmaceutical interventions, testing, and vaccine. We sought to quantify the effect of testing and vaccine strategies on the attack rate, length of the epidemic, and hospitalization.MethodsWe developed an agent-based model to simulate the dynamics of SARS-CoV-2 transmission among resident and staff agents in a nursing home. Interactions between 172 residents and 170 staff based on data from a nursing home in Los Angeles, CA. Scenarios were simulated assuming different levels of non-pharmaceutical interventions, testing frequencies, and vaccine efficacy to reduce transmission.ResultsUnder the hypothetical scenario of widespread SARS-CoV-2 in the community, 3-day testing frequency minimized the attack rate and the time to eradicate an outbreak. Prioritization of vaccine among staff or staff and residents minimized the cumulative number of infections and hospitalization, particularly in the scenario of high probability of an introduction. Reducing the probability of a viral introduction eased the demand on testing and vaccination rate to decrease infections and hospitalizations.ConclusionsImproving frequency of testing from 7-days to 3-days minimized the number of infections and hospitalizations, despite widespread community transmission. Vaccine prioritization of staff provides the best protection strategy when the risk of viral introduction is high.

BackgroundIn recent years, Canadian provinces have been discussing, implementing, and tightening vaccination "mandate" policies for school enrolment. British Columbia (BC), Canada's westernmost province, implemented a Vaccination Status Reporting Regulation (VSRR) in September 2019, which requires the vaccination status of children in public, private, and home schooling be reported to a provincial vaccination registry and education for parents who refuse to vaccinate. Legal vaccination mandates can carry the risk of backlash, thereby making it important to monitor public attitudes across policy implementation windows. The present study aimed to evaluate public support for this new provincial mandate following implementation.MethodsAn online panel of BC adults (n = 1301) was surveyed about 15 vaccine-promotion policy options in April 2020 following mandate implementation. Respondents were representative of the provincial population by gender, age, geographic residence, and percentage of households with children younger than 19 years of age. Poisson regression was used to estimate predictors of policy endorsement, and support for the VSRR.ResultsStrong support existed for the VSRR with 88.2% of respondents agreeing or strongly agreeing that parents should be required to provide their children's immunization records at school entry, and 74.6% supporting required education sessions for parents who refuse to vaccinate their children. Overall, the sample was supportive of vaccination, and pro-vaccine attitudes were associated with strong agreement for nearly all vaccine policy options. Policies to impose rewards (e.g., tax credits) and penalties (e.g., fines) were the least likely to receive strong agreement from respondents.ConclusionsNear the end of the first school year in British Columbia subject to the Vaccination Status Reporting Regulation, support for both the mandated documentation and mandated education elements of the policy are high, and associated with pro-vaccine attitudes. There are not marked differences in strong support based on gender, age, parenting, education level, or income.

BackgroundPeople who inject drugs (PWID) face increased risk of SARS-CoV-2 acquisition and severe disease, yet COVID-19 vaccine uptake has been suboptimal. To inform vaccination interventions tailored for the needs of this population, we explored COVID-19 vaccination acceptability and experiences among PWID in San Diego County, USA.MethodsFrom September-November 2021, we conducted qualitative interviews with PWID aged ≥18 years who were participating in a prospective study of infectious disease risks in San Diego. Thematic analysis of coded interview transcripts focused on identifying barriers and facilitators to COVID-19 vaccination.ResultsOf 28 participants, 15 reported having had ≥1 dose of COVID-19 vaccine, primarily received through community health centers, pharmacies, jails, and homeless shelters. We identified three key barriers to COVID-19 vaccination: (1) low perceived risk of COVID-19 (or belief in natural immunity), (2) institutional distrust (e.g., of pharmaceutical companies and government agencies that "rushed" vaccine development, approval, and distribution), and (3) conflicting information from news, social media, and peers. We also identified three key facilitators of vaccination, including (1) heightened personal and interpersonal safety concerns, (2) health service outreach efforts to make vaccines more accessible, and (3) tailored information delivered by trusted sources (e.g., outreach or community health workers).ConclusionsTailored intervention strategies to increase acceptability and uptake of COVID-19 vaccination among PWID should involve efforts to increase vaccine literacy and motivation while decreasing institutional distrust and structural barriers to access.

Distributing scarce resources such as COVID-19 vaccines is often a highly time-sensitive and mission-critical operation. Our research was prompted by a significant obstacle that the United States and other nations encountered during the early months of the COVID-19 vaccination campaign: Most COVID-19 vaccines require two doses given 3 or 4 weeks apart. Given the severely limited supply and mounting pressure on many countries to reduce hospitalizations and mortality, how to effectively roll out two-dose vaccines was a critical policy decision. In this paper, we first model and analyze inventory dynamics of the rollout process under three rollout strategies: (1) holding back second doses, (2) releasing second doses, and (3) stretching the lead time between doses. Then we develop an SEIR (susceptible, exposed, infectious, recovered) model that incorporates COVID-19 asymptomatic and symptomatic infections to evaluate these strategies in terms of infections, hospitalizations, and mortality. Among our findings, we show releasing second doses reduces infections but creates uneven vaccination patterns. In addition, to ensure second doses are given on time without holding back inventory, strictly less than half of the supply can be allocated to first-dose appointments. Stretching the between-dose lead time flattens the infection curve and reduces both hospitalizations and mortality compared with the strategy of releasing second doses. We also consider an alternative single-dose vaccine with lower efficacy and show that the vaccine can be more effective than its two-dose counterparts in reducing infections and mortality. We conduct extensive sensitivity analyses related to age composition, risk-based prioritization, supply disruptions, and disease transmissibility. Our paper provides important implications for policymakers to develop effective vaccine rollout strategies in developed and developing countries alike. More broadly, our paper sheds light on how to develop effective operations strategies for distributing time-sensitive resources in times of crisis.

COVID-19 vaccination in the Democratic Republic of the Congo (DRC) began in April 2021. A month later, most COVID-19 vaccine doses were reallocated to other African countries, due to low vaccine uptake and the realization that the doses would expire before use. Based on data available on 13 August 2022, 2.76% of the DRC population had been fully vaccinated with last dose of primary series of COVID-19 vaccine, placing the country second to last in Africa and in the last five in global COVID-19 vaccination coverage. The DRC's reliance on vaccine donations requires continuous adaptation of the vaccine deployment plan to match incoming COVID-19 vaccines shipments. Challenges in planning vaccine deployments, vaccinating priority populations, coordinating, and implementing the communications plan, disbursing funds, and conducting supervision of vaccination activities have contributed to low COVID-19 vaccine coverage. In addition, the spread of rumors through social media and by various community and religious leaders resulted in high levels of vaccine hesitancy. A strong risk communication and community engagement plan, coupled with innovative efforts to target the highest-risk populations are critical to increase vaccine uptake during the next phase of COVID-19 vaccine introduction.

Cancer vaccines have been shown clinically to drive tumor-reactive cell activation, proliferation, and effector function. Unfortunately, tumor eradication by treatment with cancer vaccines has been unsuccessful in many patients. Critical steps are under way to improve vaccine efficacy and combine them with immunotherapy and standard-of-care treatments.

The uptake rate of COVID-19 vaccines among children remains low in the U.S. This study aims to 1) identify sociodemographic and behavioral factors influencing parental refusal of vaccinating children, and 2) quantify the relative importance of vaccine characteristics in parental hesitancy of vaccinating children. An online survey was conducted from October to November 2021 among a probability-based, representative sample of 1456 parents with children under age 18. The survey included a discrete choice experiment asking parents to choose between two hypothetical COVID-19 vaccine alternatives with varying levels of characteristics in 10 hypothetical scenarios. Logistic regressions were used to estimate parental refusal (refused to choose any vaccine alternatives in all hypothetical scenarios) and random parameter logit regressions were used to estimate parental hesitancy (choice of vaccine alternatives depended on vaccine characteristics) of vaccinating children. About 20% parents refused to vaccinate children. The refusal is predicted by parents' sociodemographic characteristics, political orientation, vaccination status, and parents' and children's previous exposure with COVID-19. Among parents who were willing to consider vaccinating children, the most important vaccine characteristics are risk of severe side effects (31.2% relative importance) and effectiveness (30.7%), followed by protection duration (22.6%), local coverage (9.4%), and hospitalization rate of unvaccinated children (6.1%). Our findings imply that policymakers and public health professionals could develop outreach programs at community level to encourage specific subgroups and focus on vaccination depoliticization. Effectively communicating the low risk of severe side effects and high effectiveness of the vaccines may relieve some of the parental hesitancy.

BackgroundWe sought to evaluate the trends of HPV vaccination between 03/2019-09/2021 and whether the impact of the COVID pandemic on HPV vaccination varied by race/ethnicity and neighborhood deprivation index (NDI).MethodsElectronic medical records at Kaiser Permanente Southern California were used to assess monthly volume of HPV vaccine doses administered among children aged 9-12.9yrs, and up-to-date coverage (% vaccinated) by age 13 between 03/2019-09/2021. Modified Poisson models were used to evaluate the interactions between race/ethnicity, NDI and the pandemic periods on HPV vaccine coverage.ResultsHPV vaccine doses administered in 2020/2021 have returned to the 2019 level after the initial drop. The average up-to-date coverage in 05/2021-09/2021 (54.8%) remained lower than the pre-pandemic level (58.5%). The associations between race/ethnicity, NDI and HPV vaccine coverage did not vary due to the pandemic.ConclusionHPV vaccine promotion efforts are needed to address COVID-19 pandemic's lasting impact on HPV vaccination coverage.