Vaccines

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.

In October 2025, mpox virus clade I infections have been detected among men who have sex with men (MSM) in the EU/EEA, suggesting local transmission in MSM sexual networks. Given the large outbreak of mpox among MSM in 2022 and the uncertain transmission parameters of clade I in the European context, clade I poses a public health concern to the EU/EEA. This work assesses the potential effect of increasing the mpox vaccine uptake among MSM via two contributions. First, building on the European MSM and Trans Persons Internet Survey 2024, we estimate the mpox vaccine uptake among MSM as well as the proportion who are unvaccinated but willing to get vaccinated for 28 countries in the EU/EEA. Specifically, we fit Bayesian mixed-effects models for the vaccine and recovery status of an individual depending on their number of sexual partners and country. Second, we develop a susceptible-infectious-recovered model on a sexual contact network to estimate the reduction of the reproduction number if vaccines are provided to MSM who are willing to get vaccinated. Our results suggest a substantial willingness for mpox vaccination among MSM if mpox cases increase and a large reduction of the effective reproduction number if this willingness is met. These findings highlight a large potential of increasing mpox vaccine uptake among MSM and preventing future mpox outbreaks in the EU/EEA.

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.

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.

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.

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 [&ge;]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.

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.

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.

Background: The Vaccine Safety Datalink (VSD) detected a statistical signal for ischemic events (ischemic stroke or transient ischemic attack) following bivalent mRNA COVID-19 vaccination through prospective surveillance during 2022-2023. Although multiple studies from other surveillance systems and countries reported no increased risk, important methodological limitations remained. This U.S. study addressed those limitations by evaluating the ischemic stroke risk following bivalent mRNA COVID-19 vaccination, influenza vaccination, and their same-day coadministration using event-dependent self-controlled case series (SCCS) design. Methods: Study outcomes included first-ever ischemic stroke (primary outcome), first-in-1-year ischemic stroke (secondary outcome), and ischemic events (exploratory outcomes), identified using ICD-10-CM codes in inpatient and emergency department settings during September 1, 2022-March 31, 2023, among individuals aged>=12 years across eight VSD sites. Analyses were conducted separately for Pfizer-BioNTech and Moderna bivalent vaccines, with relative incidences (RI) and 95% confidence intervals (CI) estimated for 1-21-day and 1-42-day risk intervals, using person-time outside these intervals as the control period. Subgroup analyses were performed by age group (12-64, >65 years) and history of documented SARS-CoV-2 infection. Results: A total of 6,510 first-ever ischemic strokes were identified among more than 6.8 million participants. Among recipients of Pfizer-BioNTech bivalent COVID-19 and influenza vaccines, no statistically significant increased risk of first-ever ischemic stroke was observed following bivalent COVID-19 vaccination (RI=0.94; 95% CI: 0.63-1.41), influenza vaccination (RI=0.95; 95% CI: 0.82-1.10), or same-day coadministration (RI=1.15; 95% CI: 0.88-1.49) within 1-21-day risk intervals; findings were similar for 1-42-day intervals. Comparable null results were observed for Moderna vaccines and across all subgroups, secondary, and exploratory outcomes. Conclusion: No increased risk of ischemic stroke was found following bivalent mRNA COVID-19 vaccination, influenza vaccination, or their coadministration in this multi-site SCCS study. These findings are consistent with previous studies and underscore the importance of continued vaccine safety monitoring.

BackgroundVaccine-preventable diseases (VPDs) continue to impose a significant health and economic burden globally, despite advances in immunization programs. Narrower to the context of Saudi Arabia, the current literature consistently shows that the high vaccination coverage has had the primary impact of reducing disease incidence. Regardless, the broader economic impact of VPDs and the financial benefits of immunization remain important for policy evaluation within Saudi Arabia. MethodsThis study employed a model-based economic evaluation using a societal perspective in order to carry out an estimation of the economic burden of measles, influenza, and pneumococcal diseases. We utilized the Cost of Illness (COI) approach for the purpose of quantifying direct medical costs and indirect productivity losses. On the other hand, the Value of Statistical Life (VSL) approach helped in the estimation of the monetary value of mortality reduction. A comparative framework analyzed current vaccination coverage against a counterfactual no-vaccination scenario for the calculation of the return on investment (ROI). ResultsThe estimated annual economic burden of the three selected VPDs in the absence of vaccination was USD 385 (95% CI: 315-460) million. Immunization programs generated substantial economic benefits, with total benefits estimated at USD 1085 (95% CI: 815-1360) million annually. The calculated ROI was 9.0 (95% CI: 6.8-11.3), essentially an indication that for each dollar invested in vaccination, there was multiple economic returns yielded. Sensitivity analyses confirmed the robustness of these findings. ConclusionImmunization programs in Saudi Arabia provide significant economic and public health benefits and for this reason, sustained investment in vaccination is fundamentally essential towards the reduction of disease burden, improve population health, and ultimately support long-term economic productivity.

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.

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.

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.

BackgroundTo anticipate the impact of new pneumococcal vaccines and guide future updates, accurate forecasts of changes in non-vaccine serotypes (NVTs) are needed. We developed and evaluated three models that incorporated different assumptions about the way in which NVTs will increase and generated ensemble predictions for the frequency of NVTs in different post-pneumococcal conjugate vaccines (PCV) periods. MethodsWe analyzed age- and serotype-specific invasive pneumococcal disease (IPD) cases from the United States CDCs Active Bacterial Core surveillance during the pre-PCV (1998-1999), early post-PCV7 (2000-2004), late post-PCV7/pre-PCV13 (2005-2009), early post-PCV13 (2010-2014), and late post-PCV13 (2015-2019) periods. These data were augmented with IPD cases from several countries and combined with serotype-specific invasiveness to infer serotype-specific carriage prevalence. Three models ("Ranking", "Proportionate", "NFDS-lite") generated independent predictions of post-PCV IPD frequencies, which were integrated using an accuracy-weighted ensemble. Model performance was evaluated using the normalized root mean square error (NRMSE). ResultsA total of 23,959 non-PCV7 and 15,580 non-PCV13 cases were analyzed. NVT cases increased from the pre-PCV7 to the late post-PCV7 and post-PCV13 periods. The accuracy of predictions across age groups and models was consistent and high during the post-PCV13 periods but varied during the post-PCV7 periods. The Proportionate model (NRMSE=0.70-3.95) outperformed the NFDS-lite (NRMSE=0.93-8.91) and Ranking (NRMSE=1.51-5.37) models during the early-post-PCV7 period, whereas the NFDS-lite model (NRMSE=1.55-9.82) was superior to the Proportionate (NRMSE=1.45-10.22) and Ranking (NRMSE=1.86-11.35) models during the late post-PCV7 period. The Ensemble model improved on these individual models. ConclusionsThe Ensemble model offers a tool for forecasting serotype patterns to inform pneumococcal vaccines impact and future pneumococcal vaccine formulation.

IntroductionThe link between Human Papillomavirus (HPV) and cancer is well-established. In Singapore, bivalent HPV vaccines are subsidised for females, but not males. Economic analysis of HPV vaccination has generally assessed the costs to the health system, but this may not be as relevant to individual decision-making as potential lost income. We estimated the impact of bivalent HPV 16/18 vaccination on sick leave, unemployment, and premature mortality as a function of age and sex to understand the broader impact of HPV-related cancers. MethodsWe developed a population-level economic model to estimate lifetime income losses by diagnosis age, sex and cancer type. We applied sex- and cancer-specific Cox regressions to the Singapore Cancer Registry for annual predicted survival from 1992 to 2022. These were combined with census and employment data to estimate HPV-associated income losses in Singapore. Attributable fractions and vaccine effectiveness data for HPV 16/18 from the literature were used to estimate the effectiveness of bivalent HPV vaccination. Structural sensitivity analysis examined the role of 80% population coverage conferring herd immunity. ResultsThe registry contained 17,294 individuals with an HPV-associated cancer diagnosis. Lost income was greatest for cervical cancer due to its high prevalence, however the losses per diagnosis were highest for oropharyngeal cancer. Bivalent HPV vaccination led to income benefits of $SGD1,397 [$895 to $1,838] in girls and -$62 [- $76 to -$48] in boys. A gender-neutral HPV vaccination of 80% of 15-year-old Singaporeans, conferring herd immunity, would have lifetime income protective benefits of $24.4m [$14.2m, $33.7m] per cohort, a five-fold return on investment. ConclusionsIn addition to avoiding healthcare costs and lost quality of life, parents should consider vaccination as a means of avoiding potential income losses. A national policy of gender-neutral HPV vaccination could deliver substantial income protection due to both individual vaccine protection and herd immunity.

Background: Community-acquired pneumonia (CAP) remains a major global health burden disproportionately affecting older adults and people with comorbidities, with Streptococcus pneumoniae as one of the leading bacterial causes in Europe. The Hungarian Occurrence and Burden of PnEumonia (Hungarian-HOPE) study examined the incidence, hospitalization rates, and mortality of CAP between 2016 and 2020 in Hungary. Methods: The National Health Insurance Fund database was used to identify adult CAP patients (all-cause) based on ICD-10 codes J10-18. Outcomes included CAP incidence, 0-15-day hospitalization, and 0-30-day mortality after hospitalization, stratified by age, sex, and comorbidities (chronic obstructive pulmonary disease [COPD], asthma, cardiovascular disease [CVD], and type 1 and 2 diabetes [T1DM, T2DM]). Risk maps visualized relative risk gradients across population strata. Results: During the pre-pandemic period (2016-2019), over 100,000 CAP cases and more than 50,000 hospitalizations were recorded annually. In 2020, recorded cases fell to approximately 98,000, while hospitalizations increased to 66,200. Hospitalization rates increased from 25.1% in 2016 to 29.1% in 2019, then increased to 43.1% in 2020. The 30-day mortality among hospitalized patients rose from 22.7% in 2016 to 23.6% in 2019. Incidence, hospitalization, and mortality all increased with age. Relative to healthy males aged 30-39 years, CAP risk escalated steeply in the [&ge;]80 years cohort (incidence 5-15-fold; hospitalization >3-fold; mortality 11-24-fold) and was further amplified by COPD, CVD, or T2DM, with a lesser effect for T1DM. Conclusions: The results highlight the substantial age- and comorbidity-driven CAP burden in Hungary and support prioritization of preventive strategies including pneumococcal vaccination for older adults and high-risk groups.

Introduction: Synthetic oligopeptides provide a rapid and cost-efficient approach to developing antibodies and diagnostics for emerging viral variants. Methods: This study computationally and experimentally characterized a synthetic peptide analog of the SARS-CoV-2 spike subdomain 2 major disulfide loop (SD2MDL), designated S621 (CPVAIHADQLTPTWRVYSTC). Binding affinity was computationally estimated using the Heuristic Affinity Prediction Tool for Immune Complexes (HAPTIC), while experimental validation was performed using enzyme-linked immunosorbent assay (ELISA) with rabbit-derived antipeptide antibodies. Clinical diagnostic accuracy testing was done using plasma samples from RT-PCR-confirmed COVID-19 patients and pre-COVID-19 controls. Results: S621 demonstrated nanomolar binding affinity (Kdapp = 1.14 nM) and high avidity (3.67 nM), closely matching HAPTIC predictions (3.54 nM). Diagnostic evaluation yielded a sensitivity of 89.92% and specificity of 27.79%, corresponding to an overall accuracy of 71.79%. Discussion: These findings demonstrate that a single synthetic peptide derived from a conserved spike subdomain can function as a high-affinity surrogate for full-length antigens, supporting its potential application in rapid peptide-based immunodiagnostics.

BackgroundIntrauterine inflammation, commonly presenting as chorioamnionitis, is variably linked to preterm birth, neonatal infections and postnatal chronic inflammatory disorders. However, the effects of systemic maternal inflammation on exposed fetuses and offspring are less clear. We previously reported inflammatory responses in murine pups born after brief gestational exposure to experimental maternal inflammation. These findings led us to hypothesize that fetal exposure to maternal inflammation could lead to persistent alterations in postnatal immunity. ObjectiveTo test our hypothesis, we examined immune responses to vaccination, a useful measure of immune status, in young adult offspring with late gestational exposure to maternal LPS. Design/MethodsLate-gestation pregnant dams were treated with LPS or saline. Offspring (LPS-exposed or saline controls) were either immunized with the Tdap vaccine or remained unimmunized (naive mice), and were subsequently infected with Bordetella pertussis. Lung and spleen immune responses were assessed by multi-parameter flow cytometry, protein microarray and RT-PCR. ResultsWe observed that young adult (7 week old) mice exposed to maternal LPS during gestation, vaccinated with TDaP, and subsequently infected with pertussis exhibited lower lung neutrophil but higher CD4+ lymphocyte proportions relative to unexposed controls. In splenic studies, LPS-exposed mice had lower frequencies of CD4+IFN{psi}+ (Th1) and CD4+IL-17+ (Th17) cell populations. In vitro studies of post-vaccination responses to heat-killed B. pertussis showed variable levels of IL-2 and IL-4 in splenic cultures from LPS-exposed vs. control mice. Vaccinated, LPS-exposed mice showed variable splenic Stat3 and NFkb gene expression levels relative to those of naive LPS-exposed mice. ConclusionOur present murine studies show that experimental maternal inflammation during late gestation can alter immune response patterns to secondary challenge in young adult offspring. However, whether such intrauterine inflammatory exposure might also influence protective immune function remains to be determined. Our findings lead us to speculate that fetal exposure to systemic maternal inflammation in humans could have long-term implications for protective immunity.

Research on under-vaccination often segments populations using demographic or administrative variables that are operationally useful but fail to capture identity dimensions relevant to vaccination decisions. Drawing on social identity theory, we propose an identity-landscape approach distinguishing identity membership, identity centrality, and multidimensional identity structure. Using a cross-sectional survey of 1,000 UK parents, we measured 65 identity indicators, identity-importance ratings, and their association with attitudinal and behavioural hesitancy toward childhood vaccination using validated scales. Beyond established socio-demographic predictors, alternative-medicine and natural-lifestyle identities, as well as affiliation with social media networks, were linked to greater hesitancy. Greater centrality of religion and political affiliation within personal identity was also associated with higher hesitancy. Principal component analysis suggested that individuals actively engaged across multiple societal issues were more hesitant, whereas stereotypically male-gendered engagement was associated with lower hesitancy. An identity-focused population segmentation may identify previously unrecognized undervaccinated groups and inform innovative tailored immunization campaigns.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition associated with pediatric SARS-CoV-2 infection. While COVID-19 vaccines prevent infection and reduce severity, less conclusive evidence exists regarding their role in preventing MIS-C during breakthrough infections. This systematic review assessed the impact of SARS-CoV-2 vaccination on MIS-C risk during breakthrough infection. Cross-sectional studies, surveillance studies, and cohort studies were included. Of the 944 studies identified, 6 were included. A significant protective effect was seen in patients who received two doses of SARS-CoV-2 vaccination after exclusion of a biased sample (d= 0.71 [95% CI 0.07 to 1.35; p=0.03]). A trend towards a protective effect was seen after one dose of vaccination, but this effect was not statistically significant. Current literature supports a protective effect of two doses of SARS-CoV-2 vaccination against development of MIS-C in breakthrough COVID-19. The evidence supports clinician advocacy for continued vaccination of children against SARS-CoV-2.