Human Vaccines & Immunotherapeutics

We aimed to study the stability of a {beta}-SARS-CoV-2 virus-like particle (VLP) vaccine in a series of preliminary experiments using select stabilising excipients. {beta}-SARS-CoV-2 VLPs were produced and purified using established methodologies. The thermostability of VLPs was tested at 4{degrees}C and -30{degrees}C in the presence or absence of stabilizers polysorbate 80, sorbitol or L-histidine in the presence of a physiological NaCl concentration of 137mM. The integrity of VLPs was assessed using ELISA, Western immunoblot and dynamic light scatter (DLS). {beta}-SARS-CoV-2 VLPs were stable at 4{degrees}C for 14 days and the addition of stabilizing excipients improved stability compared to VLPs in PBS alone. Storage of VLPs at -80{degrees}C maintained particle integrity by DLS analysis for up to 2 years. Excipients helped to maintain the immunogenicity of the VLPs by ELISA and Western immunoblot and DLS analysis revealed that VLPs retained their particulate structure. ImportanceSARS-CoV-2 continues to circulate globally and cause significant illness. The problem of waning immunity to mRNA/LNPs has necessitated frequent boosters to keep pace of emerging variants. The development of alternative vaccines therefore remans a priority. Protein based vaccines, like VLPs, offer a safe alternative able to produce longer lasting immune responses. In this preliminary stability analysis, the {beta}-SARS-CoV-2 VLPs were found to be stable at 4{degrees}C and the addition of excipients improved VLP stability. Storage of VLPs at -30{degrees}C and -80{degrees}C also showed that the VLPs are stable for very long periods. Our findings will be of importance for the ongoing development of a SARS-CoV-2 VLP based vaccine.

West Nile virus (WNV) is the causative agent of fatal West Nile encephalitis. To date, no human vaccine against WNV has been approved. Adjuvants are important for developing effective and affordable vaccines that enhance the immunogenicity and decrease the required antigen doses. In this study, we assessed the efficacy of AddaS03, a synthetic adjuvant analogous to AS03, in a WNV subunit vaccine composed of soluble recombinant envelope protein (sEnv). Using a passive immunization mouse model, we defined the neutralizing antibody titer threshold required for protection against lethal WNV infections and applied this threshold as a surrogate marker to evaluate adjuvant efficacy. AddaS03-adjuvanted formulations elicited markedly higher neutralizing antibody titers compared to Alhydrogel adjuvant 2% (Alhydrogel), even at suboptimal antigen doses, and consistently exceeded the defined protective threshold titer. Moreover, in a sequential challenge mouse model, AddaS03-adjuvanted vaccines completely protected mice from symptomatic WNV infections, whereas Alhydrogel-adjuvanted vaccines failed to confer full protection. Collectively, these findings demonstrate that AddaS03 is a promising adjuvant for WNV subunit vaccine development and highlights the utility of a passive immunization model for defining protective antibody thresholds as a surrogate marker for vaccine evaluation.

BackgroundCoxsackie B viruses cause acute infections and have been linked to chronic diseases like cardiomyopathies, type 1 diabetes, and celiac disease. Despite their clinical significance, no vaccines exist for coxsackie B virus types. PRV-101, a new candidate vaccine covering five coxsackie B virus types, showed good immunogenicity and tolerability in a phase 1 trial (PROVENT). MethodsWe conducted an extended follow-up of the PROVENT trial to assess the long-term immune response and safety of PRV-101. A total of 26 participants from the original cohort (n=32) were enrolled for additional testing approximately two years post-immunization (11 high-dose, 10 low-dose, and 5 placebo). Coxsackie B virus -specific antibody responses were measured and compared to earlier time points. ResultsPRV-101 was safe with no late adverse effects or emergence of autoantibodies linked to type 1 diabetes or celiac disease. Neutralizing virus antibodies remained elevated, with a clear dose-dependent response. In the high-dose group, antibodies against all coxsackie B virus types reached presumably protective levels, except for coxsackie B virus 2, where two participants turned seronegative. ELISA tests confirmed elevated antibody levels against coxsackie B virus proteins. DiscussionThese results suggest that PRV-101 induces durable antibody responses lasting at least two years. The findings support the continued development of PRV-101 for preventing both acute coxsackie B virus infections and chronic diseases like type 1 diabetes and celiac disease.

In the decade since the West African Ebola virus (EBOV) epidemic, several medical countermeasures against this often-fatal hemorrhagic disease have been approved by regulatory authorities for human use. This includes monoclonal antibody-based therapies and vaccines which have been stockpiled in limited quantities. One of the vaccines is based on vesicular stomatitis virus (VSV) expressing the EBOV glycoprotein (GP) as the immunogen. The vaccine is stockpiled in limited quantity for emergency use. A single high dose has been shown to rapidly protect humans within 10 days. We developed an updated version of this vaccine expressing the GP from the 2015 EBOV-Makona isolate. Here, we wanted to determine the protective efficacy within 10 days of a single moderate dose (10-fold and 1,000-fold dilution) of the updated vaccine in nonhuman primates (NHPs). As a comparator we included a 1000-fold dilution dose group of the approved vaccine expressing the EBOV-Kikwit GP. While we achieved uniform protection with the approved vaccine at the moderate dose, only 50% of the NHPs receiving the same dose of the updated vaccine expressing the EBOV-Makona GP were protected. This study highlights the importance of evaluating VSV-based vaccine stocks expressing different filovirus GPs in preclinical models prior to progression with clinical development. Our study also highlights that rapid vaccination with reduced doses still leads to protection but at the cost of "sterile" immunity raising concerns regarding EBOV persistence and potential downstream transmission. Therefore, lower vaccine doses should only be considered in cases of severe vaccine shortage.

Objectives: Influenza is a widespread acute respiratory illness posing a major public health challenge for both the National Health Service (NHS) and society, particularly among older adults. This study aimed to assess the cost-effectiveness of high-dose quadrivalent vaccine (HD-QIV) versus adjuvanted quadrivalent vaccine (aQIV) in older adults in Spain. Methods: Public health and economic benefits were evaluated using a decision-tree model considering influenza cases, GP and ED visits, hospitalizations, and influenza-related mortality. Deterministic and probabilistic sensitivity analyses addressed epidemiological and economic uncertainties. Results: From a societal perspective, HD-QIV prevented 54,039 influenza cases, 7,733 GP consultations, 1,585 ED visits, 27,398 episodes of hospitalization due to cardiorespiratory events over a single influenza season and 1,203 deaths compared to aQIV when vaccinating adults [≥]65 years old in Spain, resulting in 14,316 LYs and 12,440 QALYs gained over a lifetime horizon. The reduction in health outcomes outweighed the increase in vaccination costs, translating to a reduction in total costs with HD-QIV compared to aQIV. Therefore, vaccinating older adults in Spain with HD-QIV instead of aQIV was a dominant strategy when evaluating hospitalizations due to respiratory and cardiovascular events. HD-QIV remained dominant from a NHS perspective. Sensitivity analyses confirmed the robustness of the model. Conclusions: This analysis showed that vaccinating older adults in Spain with HD-QIV instead of aQIV would reduce influenza cases, GP and ED visits, hospitalizations, deaths, and associated costs, and thus it should be the strategy of choice in a situation of budgetary constraints from either a societal or an NHS perspective.

ObjectiveAlthough COVID-19 vaccination is important for People Living with HIV given their elevated infection and comorbidity risks, some PLHIV are hesitant to accept vaccination. Hence, we conducted a cross-sectional study in British Columbia, Canada, aimed to identify socio-economic and health-related factors predicting COVID-19 vaccine uptake and contributing to hesitancy among PLHIV. MethodsA 34-item anonymous self-administered survey was disseminated to PLHIV accessing services through HIV and AIDS-related organisations e-newsletters between November 2022 and January 2023 in British Columbia. The survey included sociodemographic information, COVID-19 factors, HIV indicators, and the Vaccine Hesitancy Scale. Descriptive and inferential statistics were conducted to detect significant associations between the sociodemographic characteristics, health-related factors and COVID-19 vaccine uptake using IBM(R) SPSS(R) 28 and significance level at p<0.05. ResultsFrom the 276 respondents (mean age 29.93{+/-}7.55), 54.7% were men, 31.6% identified as sexual minorities, and 46.7% were of indigenous origin. Approximately 40% of the respondents received at least three vaccine doses, while 82.2% received at least one dose. Vaccine hesitancy was associated with lower education, age <44, and low income. Predictors of COVID-19 vaccine uptake included age [OR=1.06, 95% CI=1.01-1.12], bachelors degree [OR=0.22, 95% CI=0.07-0.72], family/friends infected with COVID-19 [OR 3.68 95% CI=1.56 - 8.67], HIV viral load >500 copies [OR=0.20, 95% CI=0.06-0.61], belief in vaccine importance [OR= 0.51, CI=0.28-0.95], trust in Health Canadas information [OR 0.49 CI=0.29-0.83], and concerns about vaccine adverse effects [OR=0.35, CI=0.22-0.56]. Concerns about vaccine adverse effects reduced the likelihood of receiving three COVID-19 vaccine doses by 65%. ConclusionsConsiderations must be taken around specific factors that may have an impact on COVID-19 vaccination rates among PLHIV, including information about vaccine adverse effects, HIV viral load, age, and education level. This insight should guide the development of policies and interventions aimed at encouraging individuals to maintain an up-to-date vaccination status.

Background: Understanding the underlying mechanisms for differences in vaccine uptake between migrants and non-migrants is crucial in order to design targeted interventions encouraging vaccination and to ensure vaccine-related equity. Therefore, this study examined to what extent migration-related disparities in COVID-19 vaccination were associated with psychological factors, based on the established 5C model of vaccine behaviour (Confidence, Complacency, Constraints, Calculation, Collective Responsibility). Methods: Data were obtained from the German study "Corona Monitoring Nationwide - Wave 2" (RKI-SOEP-2 study), which was carried out between November 2021 and March 2022. The association between COVID-19 vaccination and migration status, while considering the psychological factors, was investigated using multivariable binary logistic regressions. A decomposition analysis (Karlson-Holm-Breen method) was conducted to examine the extent to which migration-related disparities in vaccine uptake were associated with the psychological factors of the 5C framework. Results: Migrants were less likely to be vaccinated against COVID-19 compared to non-migrants, especially participants from the Middle East and North Africa (MENA) region. Our decomposition showed that almost two-thirds of the disparities in COVID-19 vaccine uptake between migrants and non-migrants were associated with the psychological factors (first-generation: 61.2%, second-generation: 64.2%). Confidence in safety of the vaccine was the most relevant factor in the 5C framework. Furthermore, the results highlighted the importance of a differentiated analysis regarding country of origin: While the 5C model accounted for only 19.4% of the difference between participants from the MENA region and non-migrants, the proportion for participants from Eastern Europe was 73.5%, suggesting that the underlying mechanisms for the lower uptake in the MENA group need further investigation. Conclusions: Overall, migration-related disparities in COVID-19 vaccination were significantly associated with differences in psychological factors of vaccine behaviour. To increase vaccine acceptance within the heterogeneous group of migrants in general, tailored and proactive health communication interventions are needed.

Glioblastoma Multiforme (GBM) is one of the most malignant forms of brain tumor in humans, with limited treatment options and poor overall survival rates. In the present study, we employed an in-silico workflow that integrated immunoinformatics and 3D structural modelling tools to design a multi-epitope vaccine against Podoplanin (PDPN), a transmembrane glycoprotein primarily involved in tumor invasion and metastasis. The differential expression of PDPN in tumor versus normal cells was investigated using transcriptomics datasets. Once the overexpression was confirmed, it was designated as a Tumor-Associated Antigen (TAA). B-cell, CTL, and HTL epitopes were predicted and screened for antigenicity, non-allergenicity, and non-toxicity. Selected epitopes were linked with appropriate adjuvant and linker sequences to construct a vaccine candidate. Codon optimization and in silico cloning was conducted to evaluate the constructs expression in a mammalian expression vector. The 3D structure of the vaccine candidate was modelled, refined, and validated before molecular docking with immune receptors and immune simulation studies. The results indicated that proposed polypeptide, RasIC-01v, could be a potential vaccine candidate for highly vigorous and dangerous cancer like GBM. Further experimental and immunological validations would be required to validate the commercial feasibility and development of RasIC-01v. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=116 SRC="FIGDIR/small/706629v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@7485b1org.highwire.dtl.DTLVardef@1f551c1org.highwire.dtl.DTLVardef@ca871eorg.highwire.dtl.DTLVardef@6cf53d_HPS_FORMAT_FIGEXP M_FIG C_FIG

BackgroundMET overexpression is associated with poor prognosis in many solid tumors due to its central role in tumor survival, invasion, metastasis, and chemoresistance. While targeting MET with antibody-drug conjugates has shown promising results, engineered cellular immunotherapeutic approaches have not been extensively explored. Compared to conventional single-chain variable fragments (scFv), naturally occurring single-domain antibodies consisting of variable heavy chains only (VHH or nanobodies) are smaller, retain high specificity, and exhibit remarkable biochemical stability. In this study, we tested the efficacy of MET-targeting VHH-CAR-T (chimeric antigen receptor T cells). MethodsWe generated a panel of VHH-CAR-Ts using mRNA electroporation. VHH-CAR-T cells were evaluated in functional assays including cell binding avidity, cytokine production profiles, hydrogel microwell-based cellular kinetics, and in vitro cytotoxicity. We also assessed the therapeutic efficacy of VHH-CAR-T in an in vivo mouse model of metastatic triple negative breast cancer (TNBC). ResultsAmong the tested VHH, we identified those with intermediate avidity as most effective for in vitro tumor killing. VHH-CAR-Ts with CD28 costimulatory domains demonstrated augmented cytotoxicity with favorable selectivity, requiring a minimum antigen density threshold for activation. Mechanistically, VHH-CAR-Ts demonstrated low tonic signaling, high avidity, potent cytokine production, and rapid tumor killing kinetics. When administered in an mRNA format, VHH-CAR-Ts exhibited potent and prolonged control of tumor growth in an in vivo metastatic model of TNBC. ConclusionTaken together, these results demonstrate that VHH-CAR-Ts exhibit robust MET specificity and potent therapeutic efficacy both in vitro and in vivo. Thus, VHH-CAR-T cell therapy represents a promising immunotherapeutic strategy for targeting MET-overexpressing solid tumors. What is already known on this topicMET signaling is an important contributor to the aggressiveness of many solid tumors, and targeting MET by antibody-drug conjugates has shown efficacy and safety. Targeting MET by CAR-T cells has been under study, though with limited potency. What this study addsThis study is the first to demonstrate effectiveness of anti-MET VHH-CAR-T cells. Compared with other antigen binding domains, VHH-incorporated CAR-T cells show low tonic signaling, a favorable cytokine profile, and potent tumor killing. How this study might affect research, practice or policyWith the multiple advantages of VHHs including small size, stability, and low potential for tonic signaling, VHH-CAR-T cells represent a promising approach for CAR-T design against solid tumors.

BackgroundShigellosis morbidity and mortality, combined with the increase in multidrug-resistant infections make Shigella vaccine development a global imperative. Glycoconjugate vaccines that couple immunogenic O-antigen to protein derived from Shigella may provide broader protection across Shigella species and serogroups. Such an approach also circumvents immunotolerance arising from repeated use of the same carrier. Here we use bioconjugation, exploiting an oligosaccharyltransferase (OST) enzyme to couple O-antigen and carrier protein in vivo, to generate a "double-hit" Shigella glycoconjugate vaccine. MethodGlycoconjugates were synthesised in E. coli SDB1 cells expressing S. sonnei O-antigen, the OST PglS, and one of two Shigella carrier proteins. Recombinant glycoconjugate was purified using anion exchange chromatography and then used to immunise mice. Antibody responses were measured and compared by ELISA. ResultsWhen co-produced in E. coli, PglS was able to transfer the cloned S. sonnei O-antigen onto three carrier proteins, modified to accept glycans from the PglS transferase enzymes- the standard bioconjugate carrier ExoA and two immunogenic Shigella-specific outer membrane proteins, EmrK and MdtA. Production of MdtA or ExoA glycoconjugates for immunisation studies utilised successive rounds of anion exchange chromatography, to remove unglycosylated material and obtain highly purified glycoconjugate proteins for us in vaccination. Analysis of murine sera following immunisation revealed an IgG response was raised against both carrier protein and the S. sonnei O-antigen for each glycoconjugate. ConclusionA novel, conserved Shigella protein can be utilised as an effective carrier for the generation of a "double-hit", immunogenic Shigella glycoconjugate vaccine that elicits IgG responses to both carrier protein and S. sonnei O-antigen.

While vaccination conflicts have become apparent, physicians' attitudes toward those with differing views remain unclear. Through an online survey of 492 physicians and 5,252 members of the general public in Japan in February 2026, we investigated attitudes toward four vaccines (influenza, measles, HPV, and COVID-19). Intergroup bias was assessed as ingroup minus outgroup attitudes using a feeling thermometer. Multilevel regression examined associations with agreement group and physician status. Intergroup bias was significantly positive in both agreement and disagreement groups across all vaccine types, and was higher in the agreement group. Physicians exhibited higher intergroup bias than the general public. These findings indicate that vaccination conflict is bidirectional: physicians, often viewed as targets of hostility from vaccine-hesitant individuals, themselves exhibit greater intergroup bias toward those with opposing views. Interventions to raise physicians' awareness of their own bias, alongside communication strategies for vaccine-hesitant individuals, are needed.

Dengue disease remains a significant global health threat, with current vaccines exhibiting variable efficacy and safety concerns. Virus-like particles (VLPs) offer a promising alternative by mimicking native virus structures without infectious genomes. We engineered a mammalian expression plasmid encoding Dengue-1 prM and E proteins, optimized for secretion using Japanese Encephalitis virus signal sequences, and transiently expressed it in HeLa cells. Purified VLPs exhibited spherical morphology ([~]39 nm diameter) consistent with native virions, as confirmed by transmission electron microscopy. Immunization of mice with these VLPs elicited robust Dengue-1 specific IgG antibody responses. Our study demonstrates production of immunogenic Dengue-1 VLPs in HeLa cells, highlighting their potential as a vaccine candidate and a tool for serodiagnosis. Further characterization of VLP epitopes and protective efficacy is warranted to advance vaccine development. ImportanceDengue remains a significant global health challenge, with serotype 1 being one of the dominant strains causing recurrent outbreaks in Nepal. Existing vaccines demonstrate limited efficacy and pose significant safety concerns, particularly in seronegative populations. To address these limitations, this study explores virus-like particles (VLPs) as a safer alternative vaccine platform. VLPs elicit robust immunogenicity by mimicking the structure of native virus while completely lacking genetic components. This study combines DENV1 structural proteins with optimized expression systems to enhance immunogenicity. This work is particularly significant as the first dengue vaccine research conducted in Nepal, directly addressing antigenic mismatches between existing commercial vaccines and locally circulating viral strains. Furthermore, the study provides scalable platform for developing region-specific dengue vaccines for other serotypes and flaviviruses.

Pneumonia remains a leading cause of global child mortality. Following the Pneumococcal Conjugate Vaccine (PCV) introduction in Yogyakarta, Indonesia, uptake for the primary series (PCV1 and PCV2) exceeded 90%. However, PCV3 coverage remained suboptimal (60% in 2023; 75% in 2024), indicating significant dropout. This study aimed to identify determinants of PCV immunization completeness and timeliness to address this gap. We conducted a cross-sectional study using cluster sampling among 405 caregivers of children aged 13-37 months in Yogyakarta City in March 2025. Data were collected via structured digital questionnaires assessing socio-demographics, perinatal conditions, knowledge, support systems, and attitudes toward multiple injections. Multivariate logistic regression was employed to determine factors associated with PCV immunization completeness and timeliness. Of 398 participants (98.3% response rate), the majority were female (95.7%) and housewives (75.1%). The prevalence of PCV completeness was 66.3%, while timeliness was only 36.4%. Multivariate analysis revealed that acceptance of multiple injections was the strongest predictor for both completeness (aOR 49.18; 95% CI: 21.30-113.50) and timeliness (aOR 22.04; 95% CI: 6.55-74.08). Additionally, home ownership (aOR 1.93; 95% CI: 1.04-3.58) was associated with completeness, whereas high knowledge (aOR 1.85; 95% CI: 1.12-3.03) improved timeliness. Conversely, preterm birth was significantly associated with lower odds of timeliness (aOR 0.29; 95% CI: 0.09-0.88). Acceptance of multiple injections emerged as the most critical modifiable factor for both outcomes. To optimize the PCV program, health authorities should prioritize counselling strategies to alleviate parental concerns regarding multiple injections. Additionally, intensified monitoring for preterm infants is crucial to mitigate immunization delays.

Immunocastration, a non surgical strategy based on active immunization against gonadotropin-releasing hormone (GnRH), effectively suppresses steroidogenesis and spermatogenesis. However, peptide vaccines targeting poorly immunogenic antigens such as GnRH often fail to elicit robust adaptive immune responses, requiring adjuvants or carrier proteins. Previously, we introduced Coated Bacterial Vaccines (CBVs), a platform that uses chemically inactivated Gram-positive bacteria to display recombinant antigens fused to the SlpA carboxy terminal domain (dSLPA) on their surface. This system leverages natural pathogen associated molecular patterns (PAMPs) to enhance immunogenicity without additional adjuvants. In this work, we extended the application of the CBVs platform to enhance the immune response against a poorly immunogenic GnRH-based peptide vaccine. GnRH-CBVs were formulated using inactivated Bacillus subtilis var. natto coated with a recombinant GnRH tandem repeat dSLPA fusion protein and administered to male BALB/c mice. A chitosan-adjuvanted GnRH dSLPA formulation served as a positive control. GnRH-CBVs induced a strong Th2-biased humoral response, characterized by predominant IgG1 levels comparable to those achieved with chitosan. The resulting antibodies effectively neutralized endogenous GnRH, reducing steroidogenesis and spermatogenesis and inducing marked testicular histological alterations. These findings support CBVs as a promising strategy to enhance peptide vaccine immunogenicity for veterinary immunocastration.

BackgroundThe LP.8.1-containing COVID-19 mRNA vaccines were recommended for the 2025 seasonal vaccination campaigns in Europe and the United States. Safety data on these vaccines are limited. MethodsWe conducted a nationwide register-based cohort study in Denmark including all adults aged 65 years and older or at high risk of severe COVID-19 who had received previous COVID-19 vaccine doses. The study period was July 1, 2025, to December 3, 2025. We estimated incidence rate ratios using Poisson regression comparing rates of 30 adverse events within 28 days following LP.8.1-containing vaccination with reference period rates, adjusted for age, sex, region of residence, high risk of severe COVID-19, calendar time, and comorbidities. Self-controlled case series analysis was conducted as a complementary approach. ResultsAmong 1,565,697 individuals (mean age 69.5 years; 53.8% female), 958,633 received an LP.8.1-containing vaccine. Receipt of an LP.8.1-containing vaccine was not associated with a statistically significant increased rate of any of the 30 adverse events within 28 days after vaccination. The incidence rate ratio was 0.95 (95% CI, 0.86-1.06) for ischemic cardiac event, 0.83 (95% CI, 0.76-0.92) for cerebrovascular event, and 0.32 (95% CI, 0.04-2.50) for myocarditis. Results from the self-controlled case series analysis were similar. ConclusionsIn a nationwide cohort of more than 1.5 million adults, no increased risk of 30 adverse events was observed following vaccination with LP.8.1-containing COVID-19 mRNA vaccines.

Cameroon introduced Human papilloma virus vaccine (HPVV) into the routine immunization schedule in October 2020. By the end of 2022, coverage remained low. To increase coverage, Cameroon switched to a country-wide, gender-neutral vaccination (GNV) approach in 2023, coupled with a revamped delivery strategy consisting of Community Dialogues (CDs) and Periodic Intensification of Routine Immunization (PIRIs) activities in selected health districts (HDs). We assessed the impact of these programmatic changes, notably the GNV approach, on HPVV coverage. This retrospective, cross-sectional study measured the effect of GNV and CDs + PIRIs on HPVV coverage among 9-year-old girls in Cameroon (2022-2023). Data on HPVV coverage from all 203 HDs were extracted from DHIS2, and coverage was calculated at the HD level, based on the estimated population eligible of 9-year-old girls. Descriptive statistics and multiple regression models were employed to assess the impact of GNV on vaccination coverage while adjusting for CDs + PIRIs and urban/rural status. In 2023, of the 203 HDs, 115 (56.7%) conducted GNV only, 74 (36.5%) implemented GNV & CDs + PIRIs, and 75.9% (154) were classified as rural. Among age-eligible girls, there was an overall increase in HPV vaccination coverage, with coverage rising 39.2 percentage points from 2022 to 2023. Following multiple linear regression, there was a significant increase in HPVV coverage in HDs with GNV & CDs + PIRIs compared to those with no GNV and no CDs + PIRIs ({beta}:55.5%, 95%CI: 38.7, 72.3, p=0.000). Furthermore, there was a significant increase in HPVV coverage in HDs with GNV only compared to those with no GNV or no CDs + PIRIs ({beta}:28.7%, 95%CI: 12.5, 45.0 p=0.001). Overall, the GNV approach increased HPVV coverage for girls significantly, particularly when implemented alongside CDs + PIRIs.

BackgroundThe SARS-CoV-2 LP.8.1 subvariant was incorporated into the 2025-2026 U.S. COVID-19 vaccines (mRNA-1273.251 and mRNA-1283.251). We evaluated immunogenicity and safety of these vaccines against vaccine-matched and emerging variants in individuals aged [&ge;]65 and those aged 12-64 years at high-risk of severe COVID-19. MethodsData were generated from: (1) two independent, ongoing, phase 3b/4, open-label, single-arm studies in which participants received a single dose of 50-{micro}g mRNA-1273.251 (n=103; median age, 64.0 years) or 10-{micro}g mRNA-1283.251 (n=172, median age, 59.0 years) and followed through Day 29 post-vaccination; neutralizing antibodies (nAb) were measured at baseline (Day 1) and Day 29 using a pseudovirus neutralization assay against the vaccine-matched LP.8.1 variant; (2) Day 29 immunogenicity against circulating variants (BA.3.2.2, XFG, and NB.1.8.1) was assessed in a randomly selected subset; and (3) immune-escape potential was estimated using predictive modeling. Unsolicited adverse events (AEs), including serious AEs, leading to study withdrawal, and those of special interest, were monitored. ResultsBoth vaccines elicited robust nAbs at Day 29 against LP.8.1 (geometric mean fold-rise from baseline: 12-64 years, mRNA-1273.251, 26.3; mRNA-1283.251, 53.0; [&ge;]65 years, mRNA-1273.251, 15.4; mRNA-1283.251, 36.7) and circulating variants. Model-based estimates with mRNA-1273.251 were consistent with clinical data and indicated the highest responses against LP.8.1 and lower responses against BA.3.2.2. No vaccine-related AEs were reported in either study. ConclusionsmRNA-1273.251 and mRNA-1283.251 were well tolerated through Day 29 and elicited robust nAbs against vaccine-matched and circulating variants. In predictive models, BA.3.2.2 had the highest relative risk of immune escape following mRNA-1273.251 vaccination. SUMMARYLP.8.1-containing mRNA-1273.251 and mRNA-1283.251 vaccines given as a single dose were well tolerated and induced robust Day 29 neutralizing antibodies against LP.8.1 and circulating variants.

BackgroundCold chain requirements limit vaccine accessibility and deployment. SPVX02 (Stablepharma Ltd), is a lyophilised, fridge-free version of Tetadif (BB-NCIPD EAD) tetanus-diphtheria vaccine, stable for at least 18 months at temperatures up to 30{degrees}C. MethodsA multicentre, first-in-human phase 1, blinded, randomised clinical trial to evaluate the safety and tolerability of SPVX02 compared to existing approved tetanus-diphtheria (Td) vaccines was conducted. Healthy adults aged 18-55 (BMI <=32 kg/m2) who had received Td vaccination >=10 years previously were randomly assigned (1:1:1) to receive SPVX02, Tetadif, or diTeBooster (AJ Vaccines A/S). Participants and all investigatory staff were blinded to treatment allocation. Primary outcomes were incidence of adverse events during the trial period including incidence of adverse events reported in participant diaries for 7 days post-dose. Secondary outcomes were day 28 seroprotection rates. Analyses were descriptive. The trial is registered with ISRCTN (98920861). FindingsBetween April 1st and September 22nd, 2025, 120 healthy volunteers were screened and sixty participants enrolled at two of three sites. The demographic characteristics of participants were equivalent between groups. No serious adverse reactions, suspected unexpected adverse reactions, or serious adverse events occurred. Fifty-four participants experienced mild or moderate adverse events (AEs); none were severe (grade 3 or higher) AEs. Reactogenicity and tolerability profiles were similar across all groups. All participants had anti-tetanus toxoid (TT) levels >=1{middle dot}0 IU/ml at Day 28. All participants in both the SPVX02 and Tetadif groups and 19 (95%) in the diTeBooster group had anti-diphtheria (DT) toxoid levels >=0{middle dot}1 IU/ml at Day 28. InterpretationSPVX02 is safe, well tolerated, with TT and DT immunogenicity similar to approved Td vaccines. This trial provides first-in-human evidence that StablevaX (Stablepharma, UK) technology can safely reformulate an aluminium-adjuvanted vaccine stable up to 30{degrees}C for 18 months. FundingFunded by Innovate UK Smart Grant project #10083165 and Stablepharma Ltd. Research In ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for randomised controlled trials with thermostable vaccines between database inception and June 2024 using the terms ("temperature stable") OR ("thermostable") AND ("vaccin*") OR ("thermostable vaccine") with no language restrictions. We identified 33 publications which described various in vitro and in vivo studies that have been performed by researchers as part of their efforts to develop thermostable vaccines. We also identified 2 publications which described randomised, controlled clinical trials that were conducted with thermostable vaccines; (1) a phase 2 clinical trial with ROTASIL, an oral rotavirus vaccine (Isanaka et al, NEJM, 2017) which is now licenced and distributed as a refrigerated product that must be stored but must be stored at 2-8{degrees}C; and (2) a phase 1 clinical trial with a current unapproved TB vaccine candidate, ID93+GLE-SE (Sagawa et al, Nature Comms, 2023) where there is no current public information regarding vaccine tolerance to freezing. Added value of this studyThis first in human study demonstrates that the reformulated thermostable aluminium hydroxide adjuvanted tetanus-diphtheria vaccine, SPVX02, is safe, well tolerated, and can boost immune responses to tetanus and diphtheria to similar levels as approved comparator vaccines. This vaccine can be stored and distributed at room temperature and is not affected by freezing. A larger Phase 2/3 trial is now planned to confirm these findings prior to consideration for market authorisation. Implications of all the available evidenceThe evidence presented here demonstrates that StablevaX technology can be successfully utilised to reformulate a vaccine to be thermostable at room temperature for an extended period of time, without compromising reactogenicity or immunogenicity. While we present data pertaining to a single vaccine, the reformulation and lyophilisation technology underpinning SPVX02 can be applied to many liquid vaccines and biological products. The WHO Immunization Agenda 2030 sets out the global strategy to improve vaccine access in resource-limited settings, prevent vaccine wastage and to reduce the logistical, financial and environmental impact of cold chain requirements. If proven successful across a broader range of vaccine products this technology has potential to significantly benefit global health.

IntroductionDuring the COVID-19 pandemic, incarcerated populations faced heightened risk of exposure due to healthcare barriers, restrictive environments, and pre-existing health conditions. Consequently, Correctional Officers (COs) faced increased risk of COVID-19 exposure. Given the health benefits of COVID-19 vaccination and the rise in vaccine hesitancy, this study examined the relationship between COs health beliefs and COVID-19 vaccine uptake. MethodsA health beliefs survey was administered to Massachusetts-based COs (n=118). Chi-squared Automatic Interaction Detection modeling and logistic regression was utilized to analyze the survey data. ResultsCOs with higher trust in vaccines and a prior positive COVID-19 test were most likely to get vaccinated voluntarily. Those with low trust in vaccines and no previous positive COVID-19 test were least likely to receive the vaccine. ConclusionDespite the severe impact of COVID-19 in correctional settings, and the evidence of vaccine efficacy against hospitalization and death, vaccine uptake among COs remains low.

Background Ever since the COVID-19 vaccine became available, vaccinations in adolescents lagged behind adults. Whether adolescent vaccination rates were higher in states with "Minor Consent" policies remains unknown. Methods We accessed adolescent (aged 12-17) county-level vaccine administration data from the CDC (12/2020-05/2023). Our outcomes were COVID-19 vaccination counts for: 1) initial dose, 2) completed series doses, and 3) booster doses. Panel Poisson regression models with state and time random effects, seasonal fixed effects, log-population offsets, and adult vaccination rates were estimated to calculate incidence rate ratios (IRR), testing the association between residing in a state with a Minor Consent policy and COVID-19 vaccine uptake. Results Overall, for the initial dose and complete series, there was no difference in adolescent COVID-19 vaccination between states with or without Minor Consent policies. However, we found that Minor Consent policies were associated with lower COVID-19 booster doses (IRR = 0.582; 95% CI: 0.409, 0.828; p = 0.0026). This association was not found in urban counties (IRR = 0.867; CI = 0.722, 1.043; p = 0.1295), but only in rural counties (IRR = 0.541; CI = 0.401, 0.730; p < 0.0001). Conclusions Minor Consent policies were not associated with higher adolescent COVID-19 vaccination. Rather, we found that Minor Consent policies were associated with lower adolescent vaccination for booster doses in rural counties. Despite minimal evidence of impact, states continue to implement Minor Consent vaccination policies. Future research should investigate not just other vaccines, but also how Minor Consent policies impact parental trust in public health more broadly.