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BackgroundAlthough vaccines are largely effective and safe, there is variability in post-vaccination experience regarding antibody response, side effects, and affective outcomes. Vaccine mindsets, specific beliefs about the vaccine, may be associated with post-vaccination experience. This is important since mindsets are malleable and may help decrease vaccine hesitancy and improve post-vaccination experience.MethodsIn a prospective study, we measured overall positive vaccine mindset and specific mindsets regarding efficacy, body response, and side effects. We tested whether vaccine mindsets before vaccination predicted neutralizing antibody response, side effects, vaccine-related stress, and affective outcomes (general stress, sadness, and happiness). Antibody response was assessed one month and six months after participants completed a SARS-CoV-2 vaccination series. Side effect experience and affective reactions were assessed daily on the vaccination day and the subsequent five days.ResultsThere was no significant association between the aggregate vaccine mindset score and neutralizing antibody response; however, people with a more positive vaccine mindset reported fewer side effects, less same-day vaccine-related anxiety, and improved affective outcomes after vaccination. In secondary analyses, when specific mindsets were explored, the mindset that vaccine side effects are a sign of treatment efficacy predicted higher antibodies, but not side effects experience and vaccine-related anxiety. Vaccine efficacy and body-response mindsets predicted fewer side effects, vaccine-related anxiety, and improved affective outcomes after vaccination.ConclusionThese findings underscore the potential of vaccine mindsets in enhancing the overall post-vaccination experience and, in some cases, increasing antibody response.

ImportanceIncreasing influenza vaccination rates is a public health priority. One method recommended by the US Centers for Disease Control and Prevention and others is for health systems to send reminders nudging patients to be vaccinated.ObjectiveTo evaluate and compare the effect of electronic health record (EHR)-based patient portal reminders vs text message reminders on influenza vaccination rates across a health system.Design, setting, and participantsThis 3-arm randomized clinical trial was conducted from September 7, 2022, to April 30, 2023, among primary care patients within the University of California, Los Angeles (UCLA) health system.InterventionsArm 1 received standard of care. The health system sent monthly reminder messages to patients due for an influenza vaccine by portal (arm 2) or text (arm 3). Arm 2 had a 2 × 2 nested design, with fixed vs responsive monthly reminders and preappointment vs no preappointment reminders. Arm 3 had 1 × 2 design, with preappointment vs no preappointment reminders. Preappointment reminders for eligible patients were sent 24 and 48 hours before scheduled primary care visits. Fixed reminders (in October, November, and December) involved identical messages via portal or text. Responsive portal reminders involved a September message asking patients about their plans for vaccination, with a follow-up reminder if the response was affirmative but the patient was not yet vaccinated.Main outcomes and measuresThe primary outcome was influenza vaccination by April 30, 2023, obtained from the UCLA EHR, including vaccination from pharmacies and other sources.ResultsA total of 262 085 patients (mean [SD] age, 45.1 [20.7] years; 237 404 [90.6%] adults; 24 681 [9.4%] children; 149 349 [57.0%] women) in 79 primary care practices were included (87 257 in arm 1, 87 478 in arm 2, and 87 350 in arm 3). At the entire primary care population level, none of the interventions improved influenza vaccination rates. All groups had rates of approximately 47%. There was no statistical or clinically significant improvement following portal vs text, preappointment reminders vs no preappointment reminders (portal and text reminders combined), or responsive vs fixed monthly portal reminders.Conclusions and relevanceAt the population level, neither portal nor text reminders for influenza vaccination were effective. Given that vaccine hesitancy may be a major reason for the lack of impact of portal or text reminders, more intensive interventions by health systems are needed to raise influenza vaccination coverage levels.Trial registrationClinicalTrials.gov Identifier: NCT05525494.

Global control of infectious diseases depends on the continuous development and deployment of diverse vaccination strategies. Currently available live-attenuated and killed virus vaccines typically take a week or longer to activate specific protection by the adaptive immunity. The mosquito-transmitted Nodamura virus (NoV) is attenuated in mice by mutations that prevent expression of the B2 viral suppressor of RNA interference (VSR) and consequently, drastically enhance in vivo production of the virus-targeting small-interfering RNAs. We reported recently that 2 d after immunization with live-attenuated VSR-disabled NoV (NoVΔB2), neonatal mice become fully protected against lethal NoV challenge and develop no detectable infection. Using Rag1-/- mice that produce no mature B and T lymphocytes as a model, here we examined the hypothesis that adaptive immunity is dispensable for the RNAi-based protective immunity activated by NoVΔB2 immunization. We show that immunization of both neonatal and adult Rag1-/- mice with live but not killed NoVΔB2 induces full protection against NoV challenge at 2 or 14 d postimmunization. Moreover, NoVΔB2-induced protective antiviral immunity is virus-specific and remains effective in adult Rag1-/- mice 42 and 90 d after a single-shot immunization. We conclude that immunization with the live-attenuated VSR-disabled RNA virus vaccine activates rapid and long-lasting protective immunity against lethal challenges by a distinct mechanism independent of the adaptive immunity mediated by B and T cells. Future studies are warranted to determine whether additional animal and human viruses attenuated by VSR inactivation induce similar protective immunity in healthy and adaptive immunity-compromised individuals.

Melioidosis, caused by the intracellular bacterial pathogen and Tier 1 select agent Burkholderia pseudomallei (Bp), is a highly fatal disease endemic in tropical areas. No licensed vaccine against melioidosis exists. In preclinical vaccine studies, demonstrating protection against respiratory infection in the highly sensitive BALB/c mouse has been especially challenging. To address this challenge, we have used a safe yet potent live attenuated platform vector, LVS ΔcapB, previously used successfully to develop vaccines against the Tier 1 select agents of tularemia, anthrax, and plague, to develop a melioidosis vaccine. We have engineered melioidosis vaccines (rLVS ΔcapB/Bp) expressing multiple immunoprotective Bp antigens among type VI secretion system proteins Hcp1, Hcp2, and Hcp6, and membrane protein LolC. Administered intradermally, rLVS ΔcapB/Bp vaccines strongly protect highly sensitive BALB/c mice against lethal respiratory Bp challenge, but protection is overwhelmed at very high challenge doses. In contrast, administered intranasally, rLVS ΔcapB/Bp vaccines remain strongly protective against even very high challenge doses. Under some conditions, the LVS ΔcapB vector itself provides significant protection against Bp challenge, and consistent with this, both the vector and vaccines induce humoral immune responses to Bp antigens. Three-antigen vaccines expressing Hcp6-Hcp1-Hcp2 or Hcp6-Hcp1-LolC are among the most potent and provide long-term protection and protection even with a single intranasal immunization. Protection via the intranasal route was either comparable to or statistically significantly better than the single-deletional Bp mutant Bp82, which served as a positive control. Thus, rLVS ΔcapB/Bp vaccines are exceptionally promising safe and potent melioidosis vaccines.ImportanceMelioidosis, a major neglected disease caused by the intracellular bacterial pathogen Burkholderia pseudomallei, is endemic in many tropical areas of the world and causes an estimated 165,000 cases and 89,000 deaths in humans annually. Moreover, B. pseudomallei is categorized as a Tier 1 select agent of bioterrorism, largely because inhalation of low doses can cause rapidly fatal pneumonia. No licensed vaccine is available to prevent melioidosis. Here, we describe a safe and potent melioidosis vaccine that protects against lethal respiratory challenge with B. pseudomallei in a highly sensitive small animal model-even a single immunization is highly protective, and the vaccine gives long-term protection. The vaccine utilizes a highly attenuated replicating intracellular bacterium as a vector to express multiple key proteins of B. pseudomallei; this vector platform has previously been used successfully to develop potent vaccines against other Tier 1 select agent diseases including tularemia, anthrax, and plague.

The COVID-19 vaccine has been a miraculous, life-saving advance, offering staggering efficacy in adults, and was developed with astonishing speed. The time from sequencing the virus to authorizing the first COVID-19 vaccine was so brisk even the optimists appear close-minded. Yet, simultaneously, United States' COVID-19 vaccination roll-out and related policies have contained missed opportunities, errors, run counter to evidence-based medicine, and revealed limitations in the judgment of public policymakers. Misplaced utilization, contradictory messaging, and poor deployment in those who would benefit most-the elderly and high-risk-alongside unrealistic messaging, exaggeration, and coercion in those who benefit least-young, healthy Americans-is at the heart. It is important to consider the history of COVID-19 vaccines to identify where we succeeded and where we failed, and the effects that these errors may have more broadly on vaccination hesitancy and routine childhood immunization programs in the decades to come.

BackgroundElicitation of broad immune responses is understood to be required for an efficacious preventative HIV vaccine. This Phase 1 randomized controlled trial evaluated whether administration of vaccine antigens separated at multiple injection sites vs combined, fractional delivery at multiple sites affected T-cell breadth compared to standard, single site vaccination.MethodsWe randomized 90 participants to receive recombinant adenovirus 5 (rAd5) vector with HIV inserts gag, pol and env via three different strategies. The Standard group received vaccine at a single anatomic site (n = 30) compared to two polytopic (multisite) vaccination groups: Separated (n = 30), where antigens were separately administered to four anatomical sites, and Fractioned (n = 30), where fractions of each vaccine component were combined and administered at four sites. All groups received the same total dose of vaccine.FindingsCD8 T-cell response rates and magnitudes were significantly higher in the Fractioned group than Standard for several antigen pools tested. CD4 T-cell response magnitudes to Pol were higher in the Separated than Standard group. T-cell epitope mapping demonstrated greatest breadth in the Fractioned group (median 8.0 vs 2.5 for Standard, Wilcoxon p = 0.03; not significant after multiplicity adjustment for co-primary endpoints). IgG binding antibody response rates to Env were higher in the Standard and Fractioned groups vs Separated group.InterpretationThis study shows that the number of anatomic sites for which a vaccine is delivered and distribution of its antigenic components influences immune responses in humans.FundingNational Institute of Allergy and Infectious Diseases, NIH.

There is limited information on the antibody responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in subjects from developing countries with populations having a high incidence of co-morbidities. Here, we analysed the immunogenicity of homologous schemes using the ChAdOx1-S, Sputnik V, or BNT162b2 vaccines and the effect of a booster dose with ChAdOx1-S in middle-aged adults who were seropositive or seronegative to the SARS-CoV-2 spike protein before vaccination. The study was conducted post-vaccination with a follow-up of 4 months for antibody titre using enzyme-linked immunosorbent assay (ELISA) and pseudovirus (PV) neutralization assays (PNAs). All three vaccines elicited a superior IgG anti-receptor-binding domain (RBD) and neutralization response against the Alpha and Delta variants when administered to individuals with a previous infection by SARS-CoV-2. The booster dose spiked the neutralization activity among individuals with and without a prior SARS-CoV-2 infection. The ChAdOx1-S vaccine induced weaker antibody responses in infection-naive subjects. A follow-up of 4 months post-vaccination showed a drop in antibody titre, with about 20% of the infection-naive and 100% of SARS-CoV-2 pre-exposed participants with detectable neutralization capacity against Alpha pseudovirus (Alpha-PV) and Delta PV (Delta-PV). Our observations support the use of different vaccines in a country with high seroprevalence at the vaccination time.

The escalating global healthcare challenge posed by Alzheimer's Disease (AD) and compounded by the lack of effective treatments emphasizes the urgent need for innovative approaches to combat this devastating disease. Currently, passive and active immunotherapies remain the most promising strategy for AD. FDA-approved lecanemab significantly reduces Aβ aggregates from the brains of early AD patients administered biweekly with this humanized monoclonal antibody. Although the clinical benefits noted in these trials have been modest, researchers have emphasized the importance of preventive immunotherapy. Importantly, data from immunotherapy studies have shown that antibody concentrations in the periphery of vaccinated people should be sufficient for targeting Aβ in the CNS. To generate relatively high concentrations of antibodies in vaccinated people at risk of AD, we generated a universal vaccine platform, MultiTEP, and, based on it, developed a DNA vaccine, AV-1959D, targeting pathological Aβ, completed IND enabling studies, and initiated a Phase I clinical trial with early AD volunteers. Our current pilot study combined our advanced MultiTEP technology with a novel mRNA approach to develop an mRNA vaccine encapsulated in lipid-based nanoparticles (LNPs), AV-1959LR. Here, we report our initial findings on the immunogenicity of 1959LR in mice and non-human primates, comparing it with the immunogenicity of its DNA counterpart, AV-1959D.

Feline infectious peritonitis (FIP) is a devastating and often fatal disease caused by feline coronavirus (FCoV). Currently, there is no widely used vaccine for FIP, and many attempts using a variety of platforms have been largely unsuccessful due to the disease's highly complicated pathogenesis. One such complication is antibody-dependent enhancement (ADE) seen in FIP, which occurs when sub-neutralizing antibody responses to viral surface proteins paradoxically enhance disease. A novel vaccine strategy is presented here that can overcome the risk of ADE by instead using a lipid nanoparticle-encapsulated mRNA encoding the transcript for the internal structural nucleocapsid (N) FCoV protein. Both wild type and, by introduction of silent mutations, GC content-optimized mRNA vaccines targeting N were developed. mRNA durability in vitro was characterized by quantitative reverse-transcriptase PCR and protein expression by immunofluorescence assay for one week after transfection of cultured feline cells. Both mRNA durability and protein production in vitro were improved with the GC-optimized construct as compared to wild type. Immune responses were assayed by looking at N-specific humoral (by ELISA) and stimulated cytotoxic T cell (by flow cytometry) responses in a proof-of-concept mouse vaccination study. These data together demonstrate that an LNP-mRNA FIP vaccine targeting FCoV N is stable in vitro, capable of eliciting an immune response in mice, and provides justification for beginning safety and efficacy trials in cats.

The human papillomavirus (HPV) is the most common sexually transmitted infection in the United States (CDC, 2023). Although a vaccine for HPV exists, the vaccination rate in young adults is still staggeringly low. Therefore, the purpose of this study was to use Narrative Engagement Theory (NET; Miller- Day & Hecht, 2013) to examine what HPV videos young adults find most engaging and persuasive. Participants were 992 college students from a large Southwestern University who watched ten HPV videos designed to inform young adults about HPV. After each video, participants responded to questions that assessed engagement and persuasiveness and were provided space to write as much as they liked to elaborate on their answers. The results suggest that certain videos may be more effective in persuading young adults to receive the HPV vaccination.

BackgroundGiven the waning of vaccine effectiveness and the shifting of the most dominant strains in the U.S., it is imperative to understand the association between vaccination coverage and Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) disease and mortality at the community levels and whether that association might vary according to the dominant SARS-CoV-2 strains in the U.S.MethodsGeneralized estimating equations were used to estimate associations between U.S. county-level cumulative vaccination rates and booster distribution and the daily change in county-wide Coronavirus 2019 disease (COVID-19) risks and mortality during Alpha, Delta and Omicron predominance. Models were adjusted for potential confounders at both county and state level. A 2-week lag and a 4-week lag were introduced to assess vaccination rate impact on incidence and mortality, respectively.ResultsAmong 3,073 counties in 48 states, the average county population complete vaccination rate of all age groups was 50.79% as of March 11th, 2022. Each percentage increase in vaccination rates was associated with reduction of 4% (relative risk (RR) 0.9607 (95% confidence interval (CI): 0.9553, 0.9661)) and 3% (RR 0.9694 (95% CI: 0.9653, 0.9736)) in county-wide COVID-19 cases and mortality, respectively, when Alpha was the dominant variant. The associations between county-level vaccine rates and COVID-19 incidence diminished during the Delta and Omicron predominance. However, each percent increase in people receiving a booster shot was associated with reduction of 6% (RR 0.9356 (95% CI: 0.9235, 0.9479)) and 4% (RR 0.9595 (95% CI: 0.9431, 0.9761)) in COVID-19 incidence and mortality in the community, respectively, during the Omicron predominance.ConclusionsAssociations between complete vaccination rates and COVID-19 incidence and mortality appeared to vary with shifts in the dominant variant, perhaps due to variations in vaccine efficacy by variant or to waning vaccine immunity over time. Vaccine boosters were associated with notable protection against Omicron disease and mortality.

BackgroundVaccine hesitancy, delaying or refusing to vaccinate despite the availability of vaccines, impedes the progress of achieving optimal HPV vaccine coverage. Little is known about the sources of human papillomavirus (HPV) vaccine hesitancy among racially/ethnically and geographically diverse communities. The purpose of this paper is to explore HPV vaccine hesitancy among rural, Slavic, and Latino communities that reside in counties with low HPV vaccine uptake rates.MethodsKey informant interviews and focus groups were conducted with rural, Slavic, and Latino communities that reside within counties in California that have low HPV vaccine up to date rates (16-25%). Qualitative data were transcribed verbatim and analyzed using inductive and deductive thematic analysis.ResultsA total of seven focus groups and 14 key informant interviews were conducted with 39 individuals from seven California counties. Salient themes that contributed to HPV vaccine hesitancy included the following: social media and the anti-vaccination movement; a strong belief in acquiring immunity naturally; prior vaccine experiences; and vaccine timing concerns. Participants suggested the provision of culturally appropriate, in-language, in-person easy to understand HPV vaccine education to mitigate HPV vaccine hesitancy.ConclusionsOur findings can inform future interventions to increase HPV vaccine uptake among hesitant communities.

The social and behavioural determinants of COVID-19 vaccination have been described previously. However, little is known about how vaccinated people use and rate their health system. We used surveys conducted in 14 countries to study the health system correlates of COVID-19 vaccination. Country-specific logistic regression models were adjusted for respondent age, education, income, chronic illness, history of COVID-19, urban residence, and minority ethnic, racial, or linguistic group. Estimates were summarised across countries using random effects meta-analysis. Vaccination coverage with at least two or three doses ranged from 29% in India to 85% in Peru. Greater health-care use, having a regular and high-quality provider, and receiving other preventive health services were positively associated with vaccination. Confidence in the health system and government also increased the odds of vaccination. By contrast, having unmet health-care needs or experiencing discrimination or a medical mistake decreased the odds of vaccination. Associations between health system predictors and vaccination tended to be stronger in high-income countries and in countries with the most COVID-19-related deaths. Access to quality health systems might affect vaccine decisions. Building strong primary care systems and ensuring a baseline level of quality that is affordable for all should be central to pandemic preparedness strategies.

Chlamydia vaccine approaches aspire to induce Th1 cells for optimal protection, despite the fact that there is no direct evidence demonstrating Th1-mediated Chlamydia clearance from the female reproductive tract (FRT). We recently reported that T-bet-deficient mice can resolve primary Chlamydia infection normally, undermining the potentially protective role of Th1 cells in Chlamydia immunity. Here, we show that T-bet-deficient mice develop robust Th17 responses and that mice deficient in Th17 cells exhibit delayed bacterial clearance, demonstrating that Chlamydia-specific Th17 cells represent an underappreciated protective population. Additionally, Th2-deficient mice competently clear cervicovaginal infection. Furthermore, we show that sensing of IFN-γ by non-hematopoietic cells is essential for Chlamydia immunity, yet bacterial clearance in the FRT does not require IFN-γ secretion by CD4 T cells. Despite the fact that Th1 cells are not necessary for Chlamydia clearance, protective immunity to Chlamydia is still dependent on MHC class-II-restricted CD4 T cells and IL-12p40. Together, these data point to IL-12p40-dependent CD4 effector maturation as essential for Chlamydia immunity, and Th17 cells to a lesser extent, yet neither Th1 nor Th2 cell development is critical. Future Chlamydia vaccination efforts will be more effective if they focus on induction of this protective CD4 T cell population.

Medium- and high-entropy alloys (M/HEAs) mix several principal elements with near-equiatomic composition and represent a model-shift strategy for designing previously unknown materials in metallurgy1-8, catalysis9-14 and other fields15-18. One of the core hypotheses of M/HEAs is lattice distortion5,19,20, which has been investigated by different numerical and experimental techniques21-26. However, determining the three-dimensional (3D) lattice distortion in M/HEAs remains a challenge. Moreover, the presumed random elemental mixing in M/HEAs has been questioned by X-ray and neutron studies27, atomistic simulations28-30, energy dispersive spectroscopy31,32 and electron diffraction33,34, which suggest the existence of local chemical order in M/HEAs. However, direct experimental observation of the 3D local chemical order has been difficult because energy dispersive spectroscopy integrates the composition of atomic columns along the zone axes7,32,34 and diffuse electron reflections may originate from planar defects instead of local chemical order35. Here we determine the 3D atomic positions of M/HEA nanoparticles using atomic electron tomography36 and quantitatively characterize the local lattice distortion, strain tensor, twin boundaries, dislocation cores and chemical short-range order (CSRO). We find that the high-entropy alloys have larger local lattice distortion and more heterogeneous strain than the medium-entropy alloys and that strain is correlated to CSRO. We also observe CSRO-mediated twinning in the medium-entropy alloys, that is, twinning occurs in energetically unfavoured CSRO regions but not in energetically favoured CSRO ones, which represents, to our knowledge, the first experimental observation of correlating local chemical order with structural defects in any material. We expect that this work will not only expand our fundamental understanding of this important class of materials but also provide the foundation for tailoring M/HEA properties through engineering lattice distortion and local chemical order.

Vaccination is crucial for the control of tuberculosis (TB), and safe, more effective, and accessible vaccines against Mycobacterium tuberculosis (Mtb) infection are critically needed to achieve TB control milestones envisioned in the End TB Strategy. TB vaccine research and development faces numerous challenges including, but not limited to, insufficient knowledge of the most informative antigens to prioritize as potential vaccine candidates, lack of defined correlates of protection, and incomplete knowledge of anatomical and cellular locations of the Mtb-infected cell in vivo, among others. To take stock of the progress, challenges, and opportunities in TB vaccine R&D, the Stop TB Partnership Working Group on New TB Vaccines (WGNV), in partnership with the National Institute of Allergy and Infectious Diseases (NIAID) cohosted a two-day virtual workshop on 13–14 June 2023 with experts from all over the world. In this report, we summarize key themes and discussions from the meeting, highlighting progress and gaps in the TB vaccine research.

Despite widespread availability of human papillomavirus (HPV) vaccines and recommendations for routine use, awareness and uptake of HPV vaccination are not universal. We assessed self-reported history of HPV vaccination in a sample of low-income men and women recruited from the community using respondent-driven sampling as part of the National HIV Behavioral Surveillance (NHBS) survey in San Francisco. Of the 384 respondents, a minority (12.5%) reported they had received the HPV vaccine. In multivariate analysis, independent associations with HPV vaccination history were female sex (adjusted odds ratio [AOR] = 3.76, 95% confidence interval [CI] = [1.73, 8.17]), younger age (AOR = 0.89 per year, 95% CI = [0.86, 0.92]), and education above high school (AOR = 2.84, 95% CI = [1.37, 5.90]). Missed opportunities for HPV vaccination were evident in 84.4% of respondents having visited a health care provider in the last year, including 40.1% tested for a sexually transmitted infection, and entry into higher education programs (33.4%).

ObjectiveThe objective of this formative study was to gather women's perspectives in the design and communication modalities of a health kiosk set within a Planned Parenthood setting to promote patient education about the Human papillomavirus (HPV) and to motivate uptake of the HPV vaccine.MethodsTwenty-four women aged 18-35 participated in in-depth one-on-one interviews at a Planned Parenthood health center, which were analyzed in code-associated categories using NVivo11 Pro.ResultsMost women showed receptivity to using an on-site health kiosk, as well as QR codes linked to text messages, to receive HPV-related health information outside of the clinic setting and reminders. Participants provided suggestions for kiosk design and communication modalities.ConclusionsAmong low-income women we interviewed at Planned Parenthood, increasing HPV vaccination rates necessitates engaging digital health tools which incorporate both the preferences and needs of vulnerable populations.InnovationDesigning a point-of-service health kiosk that 1) draws on user preferences early in the design phase, 2) integrates multiple communication technologies, and 3) disseminates culturally grounded HPV vaccination decisions narratives that are tailored to vaccination awareness level is a promising approach in reducing barriers to HPV vaccine education and vaccine uptake among low-income women at safety-net clinics.

Human astroviruses (HAstVs) are small, non-enveloped icosahedral RNA viruses that are a significant cause of diarrhoea in young children. Despite their worldwide prevalence, HAstV pathogenesis studies and vaccine development remain challenging due to the lack of an animal model for HAstV infection. The recent development of a murine astrovirus (MuAstV) infection model in mice provides the opportunity to test proof-of-concept vaccines based on MuAstV antigens. To help establish a system in which an astrovirus capsid spike-based vaccine could be tested in vivo, we designed and produced a recombinant MuAstV capsid spike protein based on predicted secondary structure homology to HAstV spike proteins. The recombinant MuAstV spike can be expressed with high efficiency in Escherichia coli and retains antigenicity to polyclonal antibodies elicited by MuAstV infection. We determined the crystal structure of the MuAstV spike to 1.75 Å and assessed its structural conservation with HAstV capsid spike. Despite low sequence identity between the MuAstV and HAstV spikes and differences in their overall shapes, they share related structural folds. Additionally, we found that vaccination with MuAstV spike induced anti-MuAstV-spike antibodies, highlighting that the recombinant spike is immunogenic. These studies lay a foundation for future in vivo MuAstV challenge studies to test whether MuAstV spike can be the basis of an effective vaccine.

Purpose of reviewThere is growing consensus that eliciting CD8 + T cells in addition to antibodies may be required for an effective HIV vaccine for both prevention and cure. Here, we review key qualities of vaccine-elicited CD8 + T cells as well as major CD8 + T cell-based delivery platforms used in recent HIV vaccine clinical trials.Recent findingsMuch progress has been made in improving HIV immunogen design and delivery platforms to optimize CD8 + T cell responses. With regards to viral vectors, recent trials have tested newer chimp and human adenovirus vectors as well as a CMV vector. DNA vaccine immunogenicity has been increased by delivering the vaccines by electroporation and together with adjuvants as well as administering them as part of a heterologous regimen. In preclinical models, self-amplifying RNA vaccines can generate durable tissue-based CD8 + T cells. While it may be beneficial for HIV vaccines to recapitulate the functional and phenotypic features of HIV-specific CD8 + T cells isolated from elite controllers, most of these features are not routinely measured in HIV vaccine clinical trials.SummaryIdentifying a vaccine capable of generating durable T cell responses that target mutationally vulnerable epitopes and that can rapidly intercept infecting or rebounding virus remains a challenge for HIV. Comprehensive assessment of HIV vaccine-elicited CD8 + T cells, as well as comparisons between different vaccine platforms, will be critical to advance our understanding of how to design better CD8 + T cell-based vaccines for HIV.

ObjectiveWe describe the prevalence of COVID-19 vaccine uptake, substance use, and other factors associated with vaccine hesitancy among participants from nine North American cohort studies following a diverse group of individuals at risk for or living with HIV.MethodsBetween May 2021 and January 2022, participants completed a survey related to COVID-19 vaccination. Participants included those with and without substance use. Those responding as 'no' or 'undecided' to the question "Do you plan on getting the COVID-19 vaccine?" were categorized as vaccine hesitant. Differences between groups were evaluated using chi-square methods and multivariable log-binomial models were used to calculate prevalence ratios (PR) of COVID-19 vaccine hesitancy with separate models for each substance.ResultsAmong 1,696 participants, COVID-19 vaccination was deferred or declined by 16%. Vaccine hesitant participants were younger, with a greater proportion unstably housed (14.8% vs. 10.0%; p = 0.02), and not living with HIV (48.% vs. 36.6%; p

Purpose: We examined associations between vaccine confidence and COVID-19 vaccine uptake among gay, bisexual, and other men who have sex with men (GBMSM). Methods: Computer-assisted self-interviews were conducted among 249 GBMSM participating in mSTUDY from May to October 2021-a cohort of GBMSM with a history of substance use in Los Angeles. Data were collected using a vaccine confidence index. The association between vaccine confidence and COVID-19 vaccine uptake was assessed using multivariable log-binomial regression. Results: Two-thirds (64.7%) of GBMSM reported receiving at least one dose of COVID-19 vaccine. Vaccine confidence was positively associated with COVID-19 vaccine uptake. Participants expressed neutral attitudes on government trust and vaccine safety. Perceived health benefit and vaccine effectiveness were statistically significantly associated with vaccine uptake (adjusted prevalence ratio [APR] = 1.59, 95% confidence interval [CI]: 1.20-2.16; APR = 1.51, 95% CI: 1.07-2.15). Conclusions: Public health programs should prioritize public benefit and vaccine effectiveness messaging to advance vaccination among GBMSM who use substances.

Despite universal recommendations for COVID-19 mRNA vaccination in pregnancy, uptake has been lower than desired. There have been limited studies of the direct impact of COVID-19 mRNA vaccine exposure in human placental tissue. Using a primary human placental explants model, we investigated the uptake of two common mRNA vaccines (BNT162b2 Pfizer-BioNTech or mRNA-1273 Moderna), and whether exposure altered villous cytokine responses. Explants derived from second or third trimester chorionic villi were incubated with vaccines at supraphysiologic concentrations and analyzed at two time points. We observed minimal uptake of mRNA vaccines in placental explants by in situ hybridization and quantitative RT-PCR. No specific or global cytokine response was elicited by either of the mRNA vaccines in multiplexed immunoassays. Our results suggest that the human placenta does not readily absorb the COVID-19 mRNA vaccines nor generate a significant inflammatory response after exposure.

Highly effective vaccines elicit specific, robust, and durable adaptive immune responses. To advance informed vaccine design, it is critical that we understand the cellular dynamics underlying responses to different antigen formats. Here, we sought to understand how antigen-specific B and T cells were activated and participated in adaptive immune responses within the mucosal site. Using a human tonsil organoid model, we tracked the differentiation and kinetics of the adaptive immune response to influenza vaccine and virus modalities. Each antigen format elicited distinct B and T cell responses, including differences in their magnitude, diversity, phenotype, function, and breadth. These differences culminated in substantial changes in the corresponding antibody response. A major source of antigen format-related variability was the ability to recruit naive vs. memory B and T cells to the response. These findings have important implications for vaccine design and the generation of protective immune responses in the upper respiratory tract.

BackgroundWe evaluated the impact of a brief peer-led intervention on COVID-19 vaccination among people who inject drugs (PWID) presenting at syringe services program (SSP) locations in San Diego County, California.MethodsBetween March and July 2022, PWID aged ≥18 years without recent voluntary COVID-19 testing who were not up to date on COVID-19 vaccinations received a single-session motivational interviewing intervention (LinkUP) or an attention-matched didactic control condition from trained peer counselors at SSP sites randomized by week. Following either 30-minute session, counselors offered referrals to local vaccination services. Multivariable log binomial regression via generalized estimating equations assessed LinkUP effects on (1) acceptance of COVID-19 vaccination referrals immediately postintervention and (2) COVID-19 vaccine uptake at 6-month follow-up.ResultsCOVID-19 vaccination outcomes were obtained on 135 (90.6%) of 149 participants. In multivariable analysis, participants receiving LinkUP had greater acceptance of COVID-19 vaccination referrals than controls (adjusted relative risk, 3.50; 95% CI, 1.01-12.2) and were marginally more likely to report receiving a new COVID-19 vaccine dose (adjusted relative risk, 1.57; 95% CI, .99-2.48). After 6 months, 20% reported receiving a new vaccine dose; however, if COVID-19 vaccine had been available at SSPs, this proportion could have been as high as 34.3% (45.3% LinkUP vs 24.3% control; P = .01).ConclusionsA brief peer-led SSP-based intervention significantly improved COVID-19 vaccination among PWID. Further improvements could likely be obtained by supporting SSPs to offer COVID-19 vaccination on-site instead of relying on referrals.Clinical trials registrationClinicalTrials.gov NCT05181657.

COVID-19 vaccine coverage in most countries in Africa remains low. Determinants of uptake need to be better understood to improve vaccination campaigns. Few studies from Africa have identified correlates of COVID-19 vaccination in the general population. We surveyed adults at 32 healthcare facilities across Malawi, purposively sampled to ensure balanced representation of adults with and without HIV. The survey, informed by the World Health Organization's Behavioural and Social Drivers of Vaccination Framework, asked about people's thoughts and feelings about the vaccine, social processes, motivation to vaccinate, and access issues. We classified respondents' COVID-19 vaccination status and willingness to vaccinate, and used multivariable logistic regression to assess correlates of these. Among 837 surveyed individuals (median age was 39 years (IQR 30-49) and 56% were female), 33% were up-to-date on COVID-19 vaccination, 61% were unvaccinated, and 6% were overdue for a second dose. Those up-to-date were more likely to know someone who had died from COVID-19, feel the vaccine is important and safe, and perceive pro-vaccination social norms. Despite prevalent concerns about vaccine side effects, 54% of unvaccinated respondents were willing to vaccinate. Access issues were reported by 28% of unvaccinated but willing respondents. Up-to-date COVID-19 vaccination status was associated with positive attitudes about the vaccine and with perceiving pro-vaccination social norms. Over half of unvaccinated respondents were willing to get vaccinated. Disseminating vaccine safety messages from trusted sources and ensuring local vaccine availability may ultimately increase vaccine uptake.

IntroductionNovel strategies are needed to address barriers to COVID-19 vaccination among people experiencing homelessness (PEH), a population that faces increased COVID-19 risk. Although growing evidence suggests that financial incentives for vaccination are acceptable to PEH, their impact on uptake is unknown. This study aimed to assess whether offering $50 gift cards was associated with the uptake of the first doses of COVID-19 vaccine among PEH in Los Angeles County.MethodsVaccination clinics began on March 15, 2021; the financial incentive program was implemented from September 26, 2021 to April 30, 2022. Interrupted time-series analysis with quasi-Poisson regression was used to evaluate the level and slope change in the number of weekly first doses administered. Time-varying confounders included the weekly number of clinics and the weekly number of new cases. Demographic characteristics were compared for PEH vaccinated before and after the implementation of the incentive program using chi-square tests.ResultsOffering financial incentives was associated with the administration of 2.5 times (95% CI=1.8, 3.1) more first doses than would have been expected without the program. Level (-0.184, 95% CI= -1.166, -0.467) and slope change (0.042, 95% CI=0.031, 0.053) were observed. Individuals who were unsheltered, aged

Questions remain regarding the effect of baseline host and exposure factors on vaccine efficacy (VE) across pathogens and vaccine platforms. We report placebo-controlled data from four Phase 3 COVID-19 trials during the early period of the pandemic. This was a cross-protocol analysis of four randomized, placebo-controlled efficacy trials (Moderna/mRNA1273, AstraZeneca/AZD1222, Janssen/Ad26.COV2.S, and Novavax/NVX-CoV2373) using a harmonized design. Trials were conducted in the United States and international sites in adults ≥ 18 years of age. VE was assessed for symptomatic and severe COVID-19. We analyzed 114,480 participants from both placebo and vaccine arms, enrolled July 2020 to February 2021, with follow up through July 2021. VE against symptomatic COVID-19 showed little heterogeneity across baseline socio-demographic, clinical or exposure characteristics, in either univariate or multivariate analysis, regardless of vaccine platform. Similarly, VE against severe COVID-19 in the single trial (Janssen) with sufficient endpoints for analysis showed little evidence of heterogeneity. COVID-19 VE is not influenced by baseline host or exposure characteristics across efficacy trials of different vaccine platforms and countries when well matched to circulating virus strains. This supports use of these vaccines, regardless of platform type, as effective tools in the near term for reducing symptomatic and severe COVID-19, particularly for older individuals and those with common co-morbidities during major variant shifts. Clinical trial registration numbers: NCT04470427, NCT04516746, NCT04505722, and NCT04611802.

Concerns about the duration of protection conferred by coronavirus disease 2019 (COVID-19) vaccines have arisen in postlicensure evaluations. "Depletion of susceptibles," a bias driven by differential accrual of infection among vaccinated and unvaccinated individuals, may obscure vaccine effectiveness (VE) estimates, hindering interpretation. We enrolled California residents who received molecular SARS-CoV-2 tests in a matched, test-negative design, case-control study to estimate VE of mRNA-based COVID-19 vaccines between February 23 and December 5, 2021. We analyzed waning protection following 2 vaccine doses using conditional logistic regression models. Additionally, we used data from a population-based serological study to adjust for "depletion-of-susceptibles" bias and estimated VE for 3 doses, by time since second dose receipt. Pooled VE of BNT162b2 and mRNA-1273 against symptomatic SARS-CoV-2 infection was 91.3% (95% confidence interval (CI): 83.8, 95.4) at 14 days after second-dose receipt and declined to 50.8% (95% CI: 19.7, 69.8) at 7 months. Adjusting for depletion-of-susceptibles bias, we estimated VE of 53.2% (95% CI: 23.6, 71.2) at 7 months after primary mRNA vaccination series. A booster dose of BN162b2 or mRNA-1273 increased VE to 95.0% (95% CI: 82.8, 98.6). These findings confirm that observed waning of protection is not attributable to epidemiologic bias and support ongoing efforts to administer additional vaccine doses to mitigate burden of COVID-19.

Post-translationally modified N-terminally truncated amyloid beta peptide with a cyclized form of glutamate at position 3 (pE3Aβ) is a highly pathogenic molecule with increased neurotoxicity and propensity for aggregation. In the brains of Alzheimer's Disease (AD) cases, pE3Aβ represents a major constituent of the amyloid plaque. The data show that pE3Aβ formation is increased at early pre-symptomatic disease stages, while tau phosphorylation and aggregation mostly occur at later stages of the disease. This suggests that pE3Aβ accumulation may be an early event in the disease pathogenesis and can be prophylactically targeted to prevent the onset of AD. The vaccine (AV-1986R/A) was generated by chemically conjugating the pE3Aβ3-11 fragment to our universal immunogenic vaccine platform MultiTEP, then formulated in AdvaxCpG adjuvant. AV-1986R/A showed high immunogenicity and selectivity, with endpoint titers in the range of 105-106 against pE3Aβ and 103-104 against the full-sized peptide in the 5XFAD AD mouse model. The vaccination showed efficient clearance of the pathology, including non-pyroglutamate-modified plaques, from the mice brains. AV-1986R/A is a novel promising candidate for the immunoprevention of AD. It is the first late preclinical candidate which selectively targets a pathology-specific form of amyloid with minimal immunoreactivity against the full-size peptide. Successful translation into clinic may offer a new avenue for the prevention of AD via vaccination of cognitively unimpaired individuals at risk of disease.

BackgroundBlack/African Americans are receiving COVID-19 vaccines at much lower rates than whites. However, research is still evolving that explains why these vaccination rates are lower. The aim of this study was to examine the effects of the pandemic among older Black/African Americans, with an emphasis on trust and vaccine intention prior to vaccine development.MethodsData were collected between July and September 2020 from 8 virtual focus groups in Detroit, MI and San Francisco Bay Area, CA with 33 older African Americans and 11 caregivers of older African Americans with cognitive impairment, supplemented by one virtual meeting with the project's Community Advisory Board. Inductive/deductive content analysis was used to identify themes.ResultsFive major themes influenced the intention to be vaccinated: uncertainty, systemic abandonment, decrease in trust, resistance to vaccines, and opportunities for vaccination. The last theme, opportunities for vaccination, emerged as a result of interaction with our CAB while collecting project data after the vaccines were available which provided additional insights about potential opportunities that would promote the uptake of COVID-19 vaccination among older Black/African Americans. The results also include application of the themes to a multi-layer framework for understanding precarity and the development of an Integrated Logic Model for a Public Health Crisis.ConclusionsThese findings suggest that trust and culturally relevant information need to be addressed immediately to accelerate vaccine uptake among older Black/African Americans. New initiatives are needed to foster trust and address systemic abandonment from all institutions. In addition, culturally relevant public health campaigns about vaccine uptake are needed. Thus, systemic issues need immediate attention to reduce health disparities associated with COVID-19.

IntroductionCOVID-19 vaccines are safe, effective, and widely available, but many adults in the U.S. have not been vaccinated for COVID-19. This study examined the associations between behavioral and social drivers of vaccination with COVID-19 vaccine uptake in the U.S. adults and their prevalence by region.MethodsA nationally representative sample of U.S. adults participated in a cross-sectional telephone survey in August-November 2021; the analysis was conducted in January 2022. Survey questions assessed self-reported COVID-19 vaccine initiation, demographics, and behavioral and social drivers of vaccination.ResultsAmong the 255,763 respondents, 76% received their first dose of COVID-19 vaccine. Vaccine uptake was higher among respondents aged ≥75 years (94%), females (78%), and Asian non-Hispanic people (94%). The drivers of vaccination most strongly associated with uptake included higher anticipated regret from nonvaccination, risk perception, and confidence in vaccine safety and importance, followed by work- or school-related vaccination requirements, social norms, and provider recommendation (all p

As of March 31, 2023, more than 30,000 monkeypox (mpox) cases had been reported in the United States in an outbreak that has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) and transgender persons (1). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) was approved by the Food and Drug Administration (FDA) in 2019 for the prevention of smallpox and mpox via subcutaneous injection as a 2-dose series (0.5 mL per dose, administered 4 weeks apart) (2). To expand vaccine access, an Emergency Use Authorization was issued by FDA on August 9, 2022, for dose-sparing intradermal injection of JYNNEOS as a 2-dose series (0.1 mL per dose, administered 4 weeks apart) (3). Vaccination was available to persons with known or presumed exposure to a person with mpox (postexposure prophylaxis [PEP]), as well as persons at increased risk for mpox or who might benefit from vaccination (preexposure mpox prophylaxis [PrEP]) (4). Because information on JYNNEOS vaccine effectiveness (VE) is limited, a matched case-control study was conducted in 12 U.S. jurisdictions,† including nine Emerging Infections Program sites and three Epidemiology and Laboratory Capacity sites,§ to evaluate VE against mpox among MSM and transgender adults aged 18-49 years. During August 19, 2022-March 31, 2023, a total of 309 case-patients were matched to 608 control patients. Adjusted VE was 75.2% (95% CI = 61.2% to 84.2%) for partial vaccination (1 dose) and 85.9% (95% CI = 73.8% to 92.4%) for full vaccination (2 doses). Adjusted VE for full vaccination by subcutaneous, intradermal, and heterologous routes of administration was 88.9% (95% CI = 56.0% to 97.2%), 80.3% (95% CI = 22.9% to 95.0%), and 86.9% (95% CI = 69.1% to 94.5%), respectively. Adjusted VE for full vaccination among immunocompromised participants was 70.2% (95% CI = -37.9% to 93.6%) and among immunocompetent participants was 87.8% (95% CI = 57.5% to 96.5%). JYNNEOS is effective at reducing the risk for mpox. Because duration of protection of 1 versus 2 doses remains unknown, persons at increased risk for mpox exposure should receive the 2-dose series as recommended by the Advisory Committee on Immunization Practices (ACIP),¶ regardless of administration route or immunocompromise status.

Parent reminders have produced modest improvements in human papillomavirus (HPV) vaccination among adolescents. However, little prior research has compared the effectiveness and feasibility of different HPV reminder types in resource-limited settings. We conducted a quasi-experimental study (2016-2017) to evaluate the effectiveness of three parent reminder types (mailed letters, robocalls, text messages) on next-dose HPV vaccine receipt among 12-year-olds in a large Federally Qualified Health Center in Los Angeles County. Six clinics were matched into three pairs: randomly assigning one clinic within each pair to intervention and control. Intervention clinics were randomly assigned to deliver one of the three parent reminder types. We calculated rates of next-dose vaccine receipt and assessed intervention effects using logistic regression models. We calculated the proportion of each type of reminder successfully delivered as a feasibility measure. The study sample comprised 877 12-year-olds due for an HPV vaccine dose (47% female, >85% Latino). At 4-month follow-up, 23% of intervention patients received an HPV vaccine dose compared to only 12% of control patients. Overall, receipt of any reminder increased rates of the next-needed HPV vaccine compared to usual care (p = 0.046). Significant improvements were observed for text reminders (p = 0.036) and boys (p = 0.006). Robocalls were the least feasible reminder type. Text message reminders are feasible and effective for promoting HPV vaccination. Future research is needed to assess the effectiveness and feasibility of reminders compared to other vaccine promotion strategies.

COVID-19 has caused significant morbidity and mortality worldwide but also accelerated the clinical use of emerging vaccine formulations. To address the current shortcomings in the prevention and treatment of SARS-CoV-2 infection, this study developed a novel vaccine platform that closely mimics dendritic cells (DCs) in antigen presentation and T-cell stimulation in a cell-free and tunable manner. Genetically engineered DCs that express the SARS-CoV-2 spike protein (S) were chemically converted into extracellular blebs (EBs). The resulting EBs elicited potentially protective humoral immunity in vivo, indicated by the production of antibodies that potently neutralized S-pseudotyped virus, presenting EBs as a promising and safe vaccine.

Accurate documentation of state-level human papillomavirus (HPV) vaccination is required for public health planning and to inform corrective actions. To examine the representativeness of the California Immunization Registry, we compared the National Immunization Survey (NIS)-Teen, commercial HMOs in California, Medi-Cal, and California Immunization Registry data for HPV vaccine series completion. Our objectives were to evaluate the vaccine registries, compare and report their completeness, and make recommendations on how to improve and use these studies. Vaccination values were extrapolated for all adolescents aged 13 to 17 years from 2018 to 2019 from NIS-Teen, adolescents aged 13 years from 2018 to 2019 reported in the California Immunization Registry, and adolescents aged 13 years for 2018 for commercial HMOs and Medi-Cal. HPV series completion among 13-year-olds in 2018 for commercial HMOs was 50 %, Medi-Cal was 45 %, and the California Immunization Registry was 28 %, with NIS-Teen rates for 13 to 17-year-olds at 50 % in 2018 and 54 % in 2019. Both rural and urban geographic regions were found to have low completion rates of the HPV series, with trends ranging from 13 % to 45 %. The California Immunization Registry's lower HPV vaccine series completion among 13-year-olds compared to the other reporting sources is most likely due differences in reporting and data collection. Importantly, this data will serve as a comparator for future, similar studies of various sources of HPV vaccination rates following the passing of Bill-1797, which will mandate immunization reporting starting in January 2023.

Our study focused on the discovery of how vaccine hesitancy is framed in Twitter discourse, allowing us to recognize at-scale all tweets that evoke any of the hesitancy framings as well as the stance of the tweet authors towards the frame. By categorizing the hesitancy framings that propagate misinformation, address issues of trust in vaccines, or highlight moral issues or civil rights, we were able to empirically recognize their ontological commitments. Ontological commitments of vaccine hesitancy framings couples with the stance of tweet authors allowed us to identify hesitancy profiles for two most controversial yet effective and underutilized vaccines for which there remains substantial reluctance among the public: the Human Papillomavirus and the COVID-19 vaccines. The discovered hesitancy profiles inform public health messaging approaches to effectively reach Twitter users with promise to shift or bolster vaccine attitudes.

Low HPV vaccination rates among Latina young adults perpetuate HPV-associated cancer disparities. Using qualitative methods, this study explored individual, interpersonal, and community factors that influence HPV vaccine delay and refusal among Mexican- and U.S.-born Mexican American young adult women. Participants (N = 30) between 18 and 26 years old were purposively sampled from two federally qualified health centers in Orange County, California. The National Institute on Minority Health and Health Disparities research framework and narrative engagement theory guided semi-structured phone interviews coded inductively and deductively. Participants primarily attributed vaccine status to individual and interpersonal reasons. Emerging themes included low HPV vaccine knowledge, insufficient provider communication, negative perceptions about HPV and the vaccine, motherhood responsibilities, mother's communication about HPV, cultural family norms, health care access, and misinformation. Compared to U.S.-born Latinas, Mexican-born participants more frequently expressed avoiding health care discussions with family. HPV vaccine recommendations for young Mexican American women should include socioculturally tailored messages that may improve HPV vaccination acceptance and uptake.

The production of vaccines in plant cells, termed plant-made pharmaceuticals or molecular farming, is a promising technology for scalable production. Compared to mammalian cell lines, like Chinese Hamster Ovary (CHO) or bacterial cells, plants can be grown with less cost on a large scale to make vaccines antigens and therapeutics affordable and accessible worldwide. An innovative application of this alternative system is the production of vaccines in edible tissues that can be consumed orally to deliver protein antigen without any further processing. In this project, we report stable expression of amino acid sequences corresponding to the TM-1 gene of Mycoplasma gallisepticum as a candidate vaccine antigen against Chronic Respiratory Disease (CRD) in chickens using wheat seed's tissues as a production host. Molecular and immunoblotting analysis confirmed the ubiquitous expression of a recombinant 41.8-kDa protein with an expression level of 1.03 mg/g dry weight in the endosperm tissues. When orally delivered, the plant-made vaccine was effective in terms of developing antibody response in animal model i.e., chicken without any detectable weight loss. Two doses of orally delivered plant-made TM-1 vaccine candidate elicited the immune response and protective effect against MG virus challenge at the level comparable to commercially available inactivated vaccine against CRD. Our study demonstrates that plant-made vaccines are not only safe but also scalable and cost-effective with prolonged stability at room temperature.

PurposeVaccinating adults who are involved with the carceral system, particularly those aged 55 or older, is crucial to containing the COVID-19 pandemic in the USA, particularly as variants continue to emerge and spread. In this Viewpoint, the authors discuss the reasons why improving access to COVID-19 vaccine and boosters among community supervised adults, especially the aging population, is critical to mitigating the public health consequences of the COVID-19 pandemic. This study concludes by providing recommendations to enhance vaccine and booster uptake in this population, as the pandemic continues.Design/methodology/approachThis is a Viewpoint paper regarding mitigating the spread of COVID-19 by improving access to vaccine and boosters among community supervised adults, especially the aging population.FindingsA key population that has been overlooked in vaccination efforts are older adults involved in the carceral system who are living in the community (i.e. "community supervised" or people on probation or parole). Older adults on probation and parole are at high risk for SARS-CoV-2 transmission and severe disease due to numerous factors at the individual, community, social and structural levels.Originality/valueImplementation of recommendations presented in this Viewpoint will mitigate COVID-19 risk among a population that has been marginalized and overlooked, yet has been the epicenter of the COVID-19 pandemic.

ObjectiveTo provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs).MethodsThis guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation.ResultsThis guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence.ConclusionApplication of these recommendations should consider patients' individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings.

IntroductionUptake of COVID-19 vaccination remains suboptimal in the United States and other settings. Though early reports indicated that a strong majority of people were interested in receiving the COVID-19 vaccine, the association between vaccine intention and uptake is not yet fully understood. Ourobjective was todescribe predictors of vaccine uptake, and estimate the sensitivity, specificity, and predictive values of self-reported COVID-19 vaccine status compared to a comprehensive statewide COVID-19 vaccine registry.MethodsA cohort of California residents that received a molecular test for SARS-CoV-2 infection during 24 February-5 December 2021 were enrolled in a telephone-administered survey. Survey participants were matched with records in a statewide immunization registry. Cox proportional hazards model were used to compare time to vaccination among those unvaccinated at survey enrollment by self-reported COVID-19 vaccination intention.ResultsAmong 864 participants who were unvaccinated at the time of interview, 272 (31%) had documentation of receipt of COVID-19 vaccination at a later date; including 194/423 (45.9%) who had initially reported being willing to receive vaccination, 41/185 (22.2%) who reported being unsure about vaccination, and 37/278 (13.3%) who reported unwillingness to receive vaccination.Adjusted hazard ratios (aHRs) for registry-confirmed COVID-19 vaccination were 0.49 (95% confidence interval: 0.32-0.76) and 0.21 (0.12-0.36) for participants expressing uncertainty and unwillingness to receive vaccination, respectively, as compared with participants who reported being willing to receive vaccination. Time to vaccination was shorter among participants from higher-income households (aHR = 3.30 [2.02-5.39]) and who reported co-morbidities or immunocompromising conditions (aHR = 1.54 [1.01-2.36]).Sensitivity of self-reported COVID-19 vaccination status was 82% (80-85%) overall, and 98% (97-99%) among those referencing vaccination records; specificity was 87% (86-89%).ConclusionWillingness to receive COVID-19 vaccination was an imperfect predictor of real-world vaccine uptake. Improved messaging about COVID-19 vaccination regardless of previous SARS-CoV-2 infection status may help improve uptake.

The ideal vaccine against viruses such as influenza and SARS-CoV-2 must provide a robust, durable and broad immune protection against multiple viral variants. However, antibody responses to current vaccines often lack robust cross-reactivity. Here we describe a polymeric Toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant, which enhances lymph node targeting, and leads to persistent activation of immune cells and broad immune responses. When mixed with alum-adsorbed antigens, this TLR7-NP adjuvant elicits cross-reactive antibodies for both dominant and subdominant epitopes and antigen-specific CD8+ T-cell responses in mice. This TLR7-NP-adjuvanted influenza subunit vaccine successfully protects mice against viral challenge of a different strain. This strategy also enhances the antibody response to a SARS-CoV-2 subunit vaccine against multiple viral variants that have emerged. Moreover, this TLR7-NP augments antigen-specific responses in human tonsil organoids. Overall, we describe a nanoparticle adjuvant to improve immune responses to viral antigens, with promising implications for developing broadly protective vaccines.

IntroductionWe studied characteristics of COVID-19 vaccination uptake among people who inject drugs (PWID).MethodsParticipants aged ≥18 years who injected drugs ≤1 month ago were recruited into a community-based cohort from October 2020 to September 2021 in San Diego, California Poisson regression identified correlates of having had ≥1 COVID-19 vaccine dose based on semi-annual follow-up interviews through March 15, 2022.ResultsOf 360 participants, 74.7% were male, mean age was 42 years; 63.1% were Hispanic/Mexican/Latinx. More than one-third had ≥1 co-morbidity. HIV and HCV seroprevalence were 4.2% and 50.6% respectively; 41.1% lacked health insurance. Only 37.8% reported having ≥1 COVID-19 vaccine dose. None received ≥3 doses. However, of those vaccinated, 37.5% were previously unwilling/unsure about COVID-19 vaccines. Believing COVID-19 vaccines include tracking devices (adjusted incidence rate ratio [aIRR]: 0.62; 95% CI: 0.42,0.92) and lacking health insurance (aIRR: 0.60; 95% CI: 0.40,0.91) were associated with approximately 40% lower COVID-19 vaccination rates). Ever receiving influenza vaccines (aIRR: 2.16; 95%CI: 1.46, 3.20) and testing HIV-seropositive (aIRR: 2.51; 95% CI: 1.03, 6.10) or SARS-CoV-2 RNA-positive (aIRR: 1.82; 95% CI: 1.05, 3.16) independently predicted higher COVID-19 vaccination rates. Older age, knowing more vaccinated people, and recent incarceration were also independently associated with higher COVID-19 vaccination rates.ConclusionsOne year after COVID-19 vaccines became available to U.S. adults, only one third of PWID had received ≥1 COVID-19 vaccine dose. Multi-faceted approaches that dispel disinformation, integrate public health and social services and increase access to free, community-based COVID-19 vaccines are urgently needed.

The U.S. Food and Drug Administration only gave emergency use authorization of the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines for infants 6 months and older in June 2022. Yet questions regarding the durability of vaccine efficacy, especially against emerging variants, in this age group remain. We demonstrated previously that a two-dose regimen of stabilized prefusion Washington SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or purified S-2P mixed with 3M-052, a synthetic Toll-like receptor (TLR) 7/8 agonist, in a squalene emulsion (Protein+3M-052-SE) was safe and immunogenic in infant rhesus macaques. Here, we demonstrate that broadly neutralizing and spike-binding antibodies against variants of concern (VOCs), as well as T cell responses, persisted for 12 months. At 1 year, corresponding to human toddler age, we challenged vaccinated rhesus macaques and age-matched nonvaccinated controls intranasally and intratracheally with a high dose of heterologous SARS-CoV-2 B.1.617.2 (Delta). Seven of eight control rhesus macaques exhibited severe interstitial pneumonia and high virus replication in the upper and lower respiratory tract. In contrast, vaccinated rhesus macaques had faster viral clearance with mild to no pneumonia. Neutralizing and binding antibody responses to the B.1.617.2 variant at the day of challenge correlated with lung pathology and reduced virus replication. Overall, the Protein+3M-052-SE vaccine provided superior protection to the mRNA-LNP vaccine, emphasizing opportunities for optimization of current vaccine platforms. The observed efficacy of both vaccines 1 year after vaccination supports the implementation of an early-life SARS-CoV-2 vaccine.

Infection by Kaposi sarcoma-associated herpesvirus (KSHV) can cause severe consequences, such as cancers and lymphoproliferative diseases. Whole inactivated viruses (WIV) with chemically destroyed genetic materials have been used as antigens in several licensed vaccines. During KSHV productive replication, virus-like vesicles (VLVs) that lack capsids and viral genomes are generated along with virions. Here, we investigated the immunogenicity of KSHV VLVs produced from a viral mutant that was defective in capsid formation and DNA packaging. Mice immunized with adjuvanted VLVs generated KSHV-specific T cell and antibody responses. Neutralization of KSHV infection by the VLV immune serum was low but was markedly enhanced in the presence of the complement system. Complement-enhanced neutralization and complement deposition on KSHV-infected cells was dependent on antibodies targeting viral open reading frame 4 (ORF4). However, limited complement-mediated enhancement was detected in the sera of a small cohort of KSHV-infected humans which contained few neutralizing antibodies. Therefore, vaccination that induces antibody effector functions can potentially improve infection-induced humoral immunity. Overall, our study highlights a potential benefit of engaging complement-mediated antibody functions in future KSHV vaccine development. IMPORTANCE KSHV is a virus that can lead to cancer after infection. A vaccine that prevents KSHV infection or transmission would be helpful in preventing the development of these cancers. We investigated KSHV VLV as an immunogen for vaccination. We determined that antibodies targeting the viral protein ORF4 induced by VLV immunization could engage the complement system and neutralize viral infection. However, ORF4-specific antibodies were seldom detected in the sera of KSHV-infected humans. Moreover, these human sera did not potently trigger complement-mediated neutralization, indicating an improvement that immunization can confer. Our study suggests a new antibody-mediated mechanism to control KSHV infection and underscores the benefit of activating the complement system in a future KSHV vaccine.

The vast majority of seasonal influenza vaccines administered each year are derived from virus propagated in eggs using technology that has changed little since the 1930s. The immunogenicity, durability, and breadth of response would likely benefit from a recombinant nanoparticle-based approach. Although the E2 protein nanoparticle (NP) platform has been previously shown to promote effective cell-mediated responses to peptide epitopes, it has not yet been reported to deliver whole protein antigens. In this study, we synthesized a novel maleimido tris-nitrilotriacetic acid (NTA) linker to couple protein hemagglutinin (HA) from H1N1 influenza virus to the E2 NP, and we evaluated the HA-specific antibody responses using protein microarrays. We found that recombinant H1 protein alone is immunogenic in mice but requires two boosts for IgG to be detected and is strongly IgG1 (Th2) polarized. When conjugated to E2 NPs, IgG2c is produced leading to a more balanced Th1/Th2 response. Inclusion of the Toll-like receptor 4 agonist monophosphoryl lipid A (MPLA) significantly enhances the immunogenicity of H1-E2 NPs while retaining the Th1/Th2 balance. Interestingly, broader homo- and heterosubtypic cross-reactivity is also observed for conjugated H1-E2 with MPLA, compared to unconjugated H1 with or without MPLA. These results highlight the potential of an NP-based delivery of HA for tuning the immunogenicity, breadth, and Th1/Th2 balance generated by recombinant HA-based vaccination. Furthermore, the modularity of this protein-protein conjugation strategy may have utility for future vaccine development against other human pathogens.

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 .