Human Vaccines & Immunotherapeutics

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.

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.

BackgroundUnderstanding 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). MethodsData 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. ResultsMigrants 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. ConclusionsOverall, 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.

BackgroundCytokines are immunomodulatory proteins that play central roles in regulating immune responses and represent attractive targets for cancer therapy. However, as single agents, cytokines have shown limited clinical benefit due to systemic toxicities and a short in vivo half-life. Our group has focused on engineering fusion cytokines (fusokines) that couple two cytokines into a single biologic to reprogram immune cell responses by enforcing non-canonical receptor engagement and signaling. A chimeric IL-6/IL-1{beta} fusokine was engineered to test the hypothesis that enforced co-engagement of IL-6 and IL-1{beta} signaling pathways would confer a gain-of-function phenotype in T cells and promote robust anti-tumor immunity. Here, we describe the immunomodulatory properties of IL6/1 fusokine and a method to deliver this fusokine to produce inhibition of ovarian tumor growth in a pre-clinical mouse model. MethodsLentiviral vectors encoding murine or human IL6/1 were designed using Vector Builder and expressed in either HEK293, CHO or ID8-F3 (p53-/-) cells depending on the downstream experiment to be conducted. IL6/1 expression was validated by ELISA and flow cytometry. Effects of human IL6/1 (hIL6/1) on T cell function (proliferation, memory phenotype, activation induced apoptosis) were monitored by flow cytometry. For in vivo studies, ID8-F3 murine ovarian cancer cells expressing mouse IL6/1 (mIL6/1) were administered intraperitoneally (I.P.) as a cell-based therapy to C57BL/6 female mice bearing established ID8-F3 luciferase tumors. Tumor progression was monitored by bioluminescence (BLI) imaging, and overall survival was evaluated. ResultshIL6/1 significantly enhanced T cell survival and selectively promoted activation and expansion of CD45RO memory T cells. mIL6/1 expressing ID8-F3 cells (ID8IL6/1) demonstrated stable transduction and sustained cytokine secretion. In vivo, ID8IL6/1 cell therapy significantly reduced tumor growth and improved overall survival compared to control groups, with 2 of 8 mice achieving complete tumor clearance. ConclusionThese findings indicate that IL6/1 fusokine enhances T cell survival and proliferation while promoting memory responses. Engineered cancer cells (ID8-F3) expressing mIL6/1 fusokine induced a strong anti-tumor response when delivered as a therapeutic vaccine in ovarian cancer mouse model. What is already known on this topicO_LIFusokines are a class of bifunctional proteins designed to achieve synergistic immune modulation. Previous studies in our lab have shown fusokine exhibit gain-of-function immunomodulating activity. Individually, IL-6 and IL-1{beta} are recognized for their roles in promoting T-cell proliferation and effector function. However, the potential for a fused IL-6/1 fusokine to reprogram the immune system and elicit a superior anti-tumor response in vivo in ovarian cancer model is not yet studied. C_LI What this study addsO_LIThis study develops a novel fusion cytokine (fusokine), combining IL-6 and IL-1{beta}, and demonstrate robust activation of T cells. In a preclinical ovarian cancer model, engineered cancer cells expressing IL6/1 used as a therapeutic vaccine showed significant tumor reduction and improved overall survival. C_LI How this study might affect research, practice or policyO_LIThis study demonstrates that in comparison to individual cytokines, fusokines have greater potential to activate T cell function and when delivered as a cell therapy, achieve clear therapeutic efficacy in an ovarian cancer model. Further translational and clinical studies may enable the development of novel and more effective fusokine cell therapy approaches for patients with ovarian cancer. C_LI

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.

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.

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.

BackgroundInternational evidence has documented ethnic inequalities in COVID-19 vaccine uptake, but national evidence for Australia remains limited. We aimed to quantify ethnic inequalities in COVID-19 vaccine uptake in the first 6 months of 2024 and examine retrospective trends in Dose 1-4 (2021-22) across detailed ethnic groups among older adults. MethodsWe conducted a nationwide cohort study of Australian residents aged [&ge;]75 years who were not Aboriginal or Torres Strait Islander (N=2,038,522) by linking the 2021 Census, Australian Immunisation Register, death, and migration data. Age-standardized uptake of any COVID-19 vaccine dose by ethnic group was calculated (Jan 1-June 30, 2024). Stratified descriptive analyses were conducted to explore intersections between ethnicity and other key sociodemographic characteristics. Uptake of Dose 1-4 during 2021-22 was also assessed across ethnic groups. ResultsIn the first 6 months of 2024, 31.1% of the cohort received a COVID-19 vaccine. Uptake was substantially lower in several ethnic groups, including Central Asian (<10.0%, 95% CI <10.0-10.7), North African and Middle Eastern (<10.0%, 95% CI <10.0-<10.0), Pasifika (13.0%, 95% CI 11.7-14.4), and South Eastern European (10.5%, 95% CI 10.3-10.7) groups. These differences persisted even among individuals born in Australia, with higher English proficiency, higher educational attainment, and living in less disadvantaged areas. Similar inequalities were observed across earlier vaccine doses. ConclusionsSubstantial ethnic inequalities in COVID-19 vaccination uptake persist among older Australians. Reliance on country of birth, language, or socioeconomic factors alone does not fully identify groups with the lowest uptake. Incorporating more detailed ethnicity information may improve identification of under-served groups and inform more targeted and culturally appropriate vaccination strategies.

BackgroundHuman papillomavirus (HPV) vaccination is a key strategy for cervical cancer elimination. In Cameroon, HPV vaccine was introduced into the expanded program on immunization in 2020. However, synthesized evidence on vaccine acceptability is needed to guide policy. This systematic review and meta-analysis aimed to estimate the pooled prevalence of HPV vaccine awareness, willingness to vaccinate, recommendation practices, and actual uptake in Cameroon, and to identify determinants of vaccine hesitancy. MethodsWe searched PubMed, Scopus, Web of Science, Embase, Cochrane Library, and African Journals Online from studies to January 2025. Studies reporting willingness to vaccinate, awareness, recommendation, and uptake of HPV vaccine were included. Pooled prevalence estimates and odds ratios were calculated using random-effects models. Heterogeneity was assessed using the I{superscript 2} statistic. The study was reported following PRISMA 2020 guidelines and registered in PROSPERO ID: CRD420261301213. ResultsThirty-three studies were included. The pooled prevalence of willingness to vaccinate was 68.1% (95% CI: 57.4-77.2; 12 studies; n = 4,993; I{superscript 2} = 98%), while HPV vaccine awareness was 41.3% (95% CI: 28.7-55.1; 33 studies; n = 8,175 participants; I{superscript 2} = 98%). Two-thirds of participants (67.7%; 95% CI: 50.7-81.0; 8 studies; n = 1,617) reported recommending the vaccine, but actual uptake was only 22.9% (95% CI: 6.9-54.5; 9 studies; n = 9,686). Willingness significantly declined from 74.2% before 2014 to 57.5% after 2021. Healthcare workers had the highest awareness (74.5%) and willingness (77.8%). Lack of HPV knowledge was associated with nearly three-fold higher hesitancy (OR: 2.58; 95% CI: 2.06-3.22). ConclusionsDespite moderate willingness, HPV vaccine awareness and uptake remain low in Cameroon, with marked disparities across regions and populations. Addressing knowledge gaps and strengthening context-specific vaccination strategies are needed to improve coverage.

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.

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.

BackgroundEver 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. MethodsWe 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, 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. ResultsOverall, 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 (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). ConclusionsMinor 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 on the topic should investigate, not just other vaccines, but how Minor Consent policies impact parental trust in public health more broadly.

Monophosphoryl lipid A (MPLA) and the saponin-MPLA nanoparticle adjuvant (SMNP) are known immunostimulants used as adjuvants in vaccines to boost immunity. These adjuvants are under investigation for use in prophylactic and therapeutic HIV-1 vaccines. However, their effects in ART-treated people with HIV-1 (PWH) remain unclear, as chronic immune activation may reduce responses and potentially reactivate latent virus reservoirs. Here we observed that both adjuvants, MPLA and SMNP, triggered TLR4-dependent cytokine production in monocyte-derived dendritic cells (DCs), but SMNP elicited a stronger response than MPLA based on costimulatory receptor expression and cytokine production. Cytokines produced by adjuvant stimulated dendritic cells were able to induce HIV-1 transcription in a J-Lat cell model. Notably, SMNP, but not MPLA, also induced a cytokine response in PBMC from PWH, albeit lower as compared to in healthy donor PBMC. Importantly, SMNP substantially reduced the size of the inducible HIV-1 reservoir in PWH ex vivo without bystander cytotoxicity. The effect on the viral reservoir was likely caused by the cytokine production induced by SMNP, as supernatants from SMNP stimulated DCs showed a similar viral reservoir reduction. Our findings demonstrate that TLR4-targeted adjuvants, especially SMNP, can effectively induce immune activation, supporting their potential use in therapeutic vaccination. However, as reservoir reduction was observed ex vivo, further evaluation is warranted to ensure safe use of such adjuvants in PWH.

Introduction: Adenoviral vectors such as chimpanzee ChAdOx1 were selected for COVID-19 vaccines due to their low seroprevalence in humans, minimizing the impact of neutralising anti-vector immunity that could attenuate vaccine responses. However, the influence of pre-existing adenoviral immunity on vaccine response remains incompletely understood. We have previously shown that SARS-CoV-2 spike-specific T cells were enhanced in ChAdOx1 nCoV-19 vaccinated immunodeficient patients compared to mRNA-based BNT162b2. Here, we assess immune cross-reactivity between ChAdOx1 and human adenovirus 5 (HuAd5), and test the hypothesis that in antibody-deficient individuals, cross-neutralisation may be impaired, allowing bystander enhancement of SARS-CoV-2 spike-specific T cell responses following ChAdOx1 nCoV-19 vaccination. Methods: We studied healthy healthcare workers (HCWs) and immunodeficient patients (IDPs) who received homologous ChAdOx1 nCoV-19 or BNT162b2 vaccines. HCWs samples were collected pre-vaccination and 4-6 weeks after the second dose, while IDP samples were obtained 4-6 weeks after the second dose. Serum anti-HuAd5 hexon IgG was quantified using a Luminex multiplex assay, and neutralizing antibodies were assessed using a replication-deficient HuAd5-GFP virus neutralization assay with flow cytometry readout. Ex vivo ELISpot and flow cytometry assays were used to measure T cell responses to HuAd5 hexon. These data were compared with previously published ChAdOx1 nCoV-19 vaccine responses in the same cohorts. Results: HuAd5 hexon-binding IgG titres were significantly higher in ChAdOx1 nCoV-19 compared to BNT162b2 vaccine recipients in both HCWs (p = 0.0043) and IDPs (p = 0.0328). Within ChAdOx1 nCoV-19 vaccine group, titres were lower in IDPs than HCWs (p = 0.0015) but not within the BNT162b2 group (p = 0.1261). HuAd5 neutralisation titres did not differ between cohorts or vaccine groups. In ChAdOx1 nCoV-19 vaccinated IDPs and HCWs, there was a significant negative correlation between HuAd5 hexon IgG titres and SARS-CoV-2 spike-specific T cell responses. Similarly, HuAd5 neutralisation titres showed an inverse correlation with spike-specific T cell responses in ChAdOx1 nCoV-19 vaccinated IDPs and HCWs. ChAdOx1 nCoV-19 vaccination induced significantly higher frequencies of HuAd5 hexon-reactive T cells compared with BNT162b2 vaccination in IDPs (p < 0.0001), consistent with cross-reactive adenoviral T cell responses. In IDPs, HuAd5 hexon-specific T cell frequencies positively correlated with SARS-CoV-2 spike-specific T cell responses following ChAdOx1 nCoV-19 vaccination but not following BNT162b2 vaccination. Functional profiling in ChAdOx1 nCoV-19 vaccinated IDPs demonstrated expansion of HuAd5 hexon-specific CD4IFN-{gamma}TNF T cells in high SARS-CoV-2 spike responders (p = 0.0002) compared to low responders, and the frequency of these cells strongly correlated with spike-specific T cell response. Discussion: ChAdOx1 nCoV-19 has been associated with stronger T cell responses than BNT162b2 in certain populations, including immunodeficient and elderly individuals. While this has been attributed to antigen persistence and innate adjuvant effects, our findings support a mechanism whereby heterologous pre-existing adenovirus immunity modulates vaccine-induced responses. Specifically, cross-reactive HuAd5-specific T cells may enhance spike-specific T cell responses via bystander enhancement, while cross-reactive binding antibodies may exert opposing effects. An implication of this study is that vaccine protocols could incorporate therapies that suppress vector-specific or cross-reactive antibodies while preserving T cell responses especially in cases where T cell-specific responses are most desirable. Also, safe vector-based vaccines can be developed for patient groups with predominant antibody deficiency. Targeted vaccination strategy could be implemented for clinical cohorts based on immune competence.

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.

(1) Background: Brain cancer is the ninth leading cause of cancer death in the US, with approximately 76,000 newly diagnosed cases annually. Studies show that at time of diagnosis, up to six-months post-treatment, 50%-80% of brain cancer survivors (BCS) report cognitive dysfunction. Mild cognitive impairment (MCI) has gained increasing attention as a persistent disability experienced by up to 75% of all BCS, which affects memory, concentration, executive function, etc. Studies show cognitive training with computerized gaming as improving cognitive function for patients with stroke, dementia, and Parkinsons. It is of significant clinical interest to develop innovative interventions that reduce MCI. Aim: To improve cognitive performance of BCS suffering with MCI by evaluating the feasibility, acceptability and effect of a Virtual Reality Cognitive Rehabilitation Training (VR-CRT) platform during four weeks of cognitive training. (2) Methods: We employed a quasi-experimental pretest/posttest non-randomized/non-blinded single-arm design for 4 weeks, with an experimental group (n=6, after attrition) using VR-CRT. Participants were selected based on convenience sampling using the electronic medical record to identify qualified patients, guided by inclusion/exclusion criteria. Feasibility was defined by retention as >80%, with usability testing using the System Usability Scale (SUS) and NASA-TLX surveys. The Hopkins Verbal Learning Test (HVLT), Controlled Oral Word Association (COWA) test, and Trail Making A-B (TM-A/B) test were used to measure cognitive performance, comparing baseline to post week-four. (3) Results: The feasibility criteria of >80% was met. All SUS and NASA scores were in the higher index, suggesting a high degree of usability, with low workload demand. For effect, the COWA findings showed a significant improvement (41.38%), with a paired sample T-Test confirming that the participants COWA scores improved significantly from pre- to post-intervention (p = 0.03), indicating enhanced verbal fluency and executive functioning after intervention. HVLT (combined) showed improvements of 18.75% for Form A and 11.32% for Form B, which also showed a significant improvement (p = .04) in the retention discrimination index from pre- to post-test. The TM-A/B test showed an improvement (25.97%), suggesting that the participants spent less time completing both parts A and B, but was not statistically significant. (4) Conclusion: This study fulfilled our aim to demonstrate modest to significant cognitive improvement using VR-CRT with brain cancer patients with MCI. Despite the small sample size, we believe the use of virtual reality will lead to important advances for patients with MCI, particularly the frontal lobe brain region, expressed in executive function.

IntroductionSpinal Muscular Atrophy (SMA) and Duchenne Muscular Dystrophy (DMD) are progressive genetic neuromuscular disorders imposing substantial caregiving demands on families. In Pakistan, where disease-modifying therapies remain largely inaccessible, care is predominantly supportive, frequently resulting in psychological distress and diminished caregiver confidence. An individuals belief in their capacity to execute required behaviours, self-efficacy, is a recognised determinant of caregiving quality, yet evidence on caregiver self-efficacy in SMA and DMD within low-resource settings remains sparse. This study aims to evaluate the effect of a multicomponent, digitally delivered intervention on self-efficacy among primary caregivers of children with SMA and DMD in Pakistan. Methods and AnalysisThis single-group, pre-post study will recruit 30 primary caregivers of children with SMA or DMD enrolled in the Treat-NMD Registry of Pakistan. An eight-week intervention will be delivered via online support groups, comprising educational video clips, expert-led live sessions, pictorial guides, and progressively tapering audio reminders. The primary outcome, self-efficacy, will be measured using a culturally adapted, content-validated Urdu version of the DMD Caregiver Self-Efficacy Scale (DMD-CSES), assessed at baseline (T0) and eight weeks post-intervention (T1). Pre-post scores will be compared using a paired t-test or Wilcoxon signed-rank test depending on data distribution, with analyses conducted in STATA Version 17. Ethics and DisseminationEthical approval has been granted by the Ethics Review Committee of Aga Khan University (2025-11875-37040). Verbal informed consent will be obtained from all participants, with confidentiality maintained throughout. Findings will be disseminated via peer-reviewed publication, conference presentations, and shared with the Treat-NMD registry network. Trial registration numberNCT07356063, Date of registration: 11/January/2026

Background: High school students may be able to communicate health topics to peers and adults. Yet, few studies have evaluated the role of high school students in community health initiatives, making them an underutilized group for disseminating health information. We pilot tested stroke education across five high schools using varied delivery approaches as a preliminary step toward evaluating youth stroke education to improve community health. Methods: In April-May 2025, five high schools in Connecticut and New York participated in stroke education. The format was designed to fit the needs of each school and included an 8-session classroom curriculum (Derby, CT), after-school club meetings (New Haven, CT; Long Island, NY), and one large assembly (Bridgeport, CT). Developed by teachers and neurology providers, the curriculum covered stroke risk factors, symptoms, and emergency response. Students completed a 15-point assessment adapted from the validated Stroke Action Test before, immediately after, and 4-6 weeks post-intervention; data were collected between April and July 2025. Results: Of 112 students completing the pre-test, 99 (88%) completed the immediate post-test and 51 (46%) the delayed follow-up. Average scores rose from 47% pre-intervention to 75% post and 70% at 4-6 weeks. All schools scored <50% on pre-tests suggesting poor baseline stroke knowledge. Conclusion: This pilot suggests that stroke education can be delivered to high school students across varied settings and may support knowledge gains up to 6 weeks. Limitations included small sample sizes and missing follow-up data. If validated in larger studies, this adaptable, teacher-supported approach could offer a scalable public health strategy for improving community stroke preparedness.

Anti-polyethylene glycol (PEG) hyperimmune pigs, immunized against PEG, provide a sensitive experimental model for the rare anaphylactic reactions induced by mRNA-PEGylated lipid nanoparticle (LNP)-based COVID-19 vaccines, such as Comirnaty. These pseudo-allergic infusion reactions can usually be prevented or attenuated by multicomponent anti-inflammatory premedication regimens; however, no established protocol exists for mRNA-LNP-based COVID-19 vaccines. The aim of the present study was to identify an effective premedication strategy capable of preventing or attenuating these reactions in hypersensitive subjects, using the hyperimmune porcine model. We compared the protective effects of individual pretreatment components; dexamethasone, famotidine, levocetirizine, acetaminophen, diclofenac, indomethacin, by analyzing hemodynamic endpoints (systemic and pulmonary arterial pressure, pulse pressure). All tested compounds modulated Comirnaty-induced anaphylactic responses; however, only cyclooxygenase (COX) inhibitors provided complete protection against anaphylaxis and other abnormal processes. This finding is consistent with the low incidence of infusion reactions to cancer nanomedicines at the Shaare Zedek Oncology Center in Israel which uses COX-inhibitors as premedication. Given that most currently used human infusion-reaction prevention protocols do not include COX inhibitors, and that steroid-containing regimens may potentially counteract vaccine efficacy, our results suggest that COX inhibitors may offer a clinically effective standalone option or form the basis of simplified premedication regimens for preventing this life-threatening condition.

BackgroundThe 2025-2026 COVID-19 vaccine season introduced updated formulations targeting the LP.8.1 lineage. This study assessed the absolute vaccine effectiveness (aVE) of mRNA-1283 and BNT162b2 on COVID-19 outcomes in adults aged [&ge;]65 years. MethodsThis retrospective study used linked electronic health record and administrative claims data through Jan 31, 2026. Adults [&ge;]65 years who received the mRNA-1283 or BNT162b2 2025-2026 COVID-19 vaccine were matched to unvaccinated individuals. Inverse probability of treatment weighting was applied to each vaccines matched cohorts to balance covariates. Each vaccine was evaluated independently against its own unvaccinated comparator group. aVE against COVID-19 related hospitalization and medically-attended COVID-19 was estimated using Cox proportional hazards models; aVE = 100 x (1 - hazard ratio [HR]). ResultsWe identified 233,072 mRNA-1283 recipients and 422,610 BNT162b2 recipients [&ge;]65 years. The aVE (95% confidence interval) of mRNA-1283 against COVID-19 related hospitalization and medically-attended COVID-19 was 59.3% (39.0%, 72.9%) and 42.0% (35.0%, 48.3%) among adults [&ge;]65 years and 66.9% (45.9 %, 79.8%) and 50.2% (42.1%, 57.2%) in [&ge;]75 years, respectively. The aVE of BNT162b2 against COVID-19 related hospitalization and medically-attended COVID-19 was 48.3% (32.4%, 60.5%) and 41.2% (36.2%, 45.8%) in [&ge;]65 years and 45.9% (26.0%, 60.4%) and 44.0% (37.8%, 49.6%) in [&ge;]75 years, respectively. ConclusionsThis is the first real-world evidence showing that mRNA-1283 prevents COVID-19-related hospitalizations and medically attended events in vulnerable older adults at highest risk of severe disease. These findings support mRNA-1283 as an important public health tool for reducing the ongoing burden of COVID-19.