The COVID-19 pandemic had profound global health and socioeconomic impacts, necessitating rapid vaccine deployment to reduce morbidity and mortality. However, perceptions regarding vaccine safety have influenced vaccine confidence and uptake in many communities. This study explored community-reported experiences of adverse events following COVID-19 vaccination and their implications for vaccine acceptance, uptake, and public perceptions in Mitooma District, Southwestern Uganda. A qualitative cross-sectional study was conducted using focus group discussions (FGDs) among community members and leaders from seven randomly selected villages in Katenga Subcounty, Mitooma District, Southwestern Uganda. Participants were purposively selected based on their involvement, influence, or knowledge of COVID-19 vaccination-related issues. Data were collected on reported experiences following vaccination, perceptions regarding vaccine safety, and factors influencing vaccine acceptance and uptake. A total of 52 participants (male-to-female ratio, 1:1) participated in the FGDs. The median age (range) of participants was 45 (23-82) years. Most participants were Banyankole (n = 45, 86.5%), married (n = 46, 88.5%), and engaged in subsistence farming (n = 26, 50%). More than half (n = 28, 53.8%) had attained primary education as their highest level of education. Participants commonly reported experiencing symptoms after COVID-19 vaccination, ranging from mild and expected local or systemic reactions to severe or unusual experiences that they perceived as vaccine-related. The most frequently reported experiences included injection-site symptoms, fever, dizziness, and gastrointestinal symptoms. Some participants also described rare and alarming events, including perceived nerve-related problems, impotence, and deaths occurring after vaccination; however, these reports were based on participant accounts and were not clinically verified or confirmed to be causally related to COVID-19 vaccination. Concerns regarding reported adverse events, amplified by misinformation and anti-vaccine messages in local media, negatively influenced willingness among some individuals to receive additional vaccine doses. Nevertheless, overall vaccine acceptance and uptake remained high, largely attributed to fear of severe COVID-19 outcomes and previous positive experiences with immunization programs. Community perceptions of vaccine safety were shaped by both personal experiences and information circulating within communities. Engagement of community leaders and participatory approaches were important in supporting vaccination efforts. Strengthening pharmacovigilance systems, improving mechanisms for reporting and evaluating adverse events following immunization, and implementing proactive risk communication strategies are essential for addressing vaccine safety concerns and maintaining public trust.
BackgroundHepatitis B virus remains a major global public health concern, responsible for significant morbidity and mortality due to complications such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Hepatitis B virus prevalence remains high in many developing countries, including Tanzania, where it is estimated to be 7.17%. Medical students are particularly vulnerable to hepatitis B virus infection because of occupational exposure, including needle-stick injuries and contact with infected blood or body fluids during clinical training. Vaccination is the most effective preventive measure against hepatitis B virus infection; however, vaccine coverage among medical students remains suboptimal.ObjectiveThis study aimed to assess hepatitis B virus vaccine uptake and identify factors influencing vaccination among medical students in Tanzania to inform strategies for improving vaccination coverage.MethodsAn analytical cross-sectional study was conducted from March to May 2025 among undergraduate clinical-year medical students at Muhimbili University of Health and Allied Sciences in Dar es Salaam, Tanzania, to assess hepatitis B virus vaccine uptake and its associated factors. A total of 343 students participated in the study. Data were collected using a structured questionnaire. Descriptive statistics were used to determine vaccination coverage, and regression analysis was performed using Statistical Package for the Social Sciences (International Business Machines Corporation) version 28 to identify factors associated with vaccine uptake. Ethical approval was obtained from the Muhimbili University of Health and Allied Sciences Institutional Review Board, and written informed consent was obtained from all participants before data collection. Participants' confidentiality and anonymity were ensured throughout the study.ResultsAmong the 343 participants, most were aged 20-24 years (61.8%), were male (65.0%), and were in their fifth (final) year of study (53.4%). Overall, 78.1% had received at least one dose of the hepatitis B vaccine, but only 42.2% had completed the full vaccination schedule. The main reason for incomplete vaccination was awaiting subsequent doses (75%). Approximately all students (98%) had been informed about the importance of hepatitis B vaccination. Multivariable analysis showed that female sex (adjusted odds ratio = 1.99, p = 0.014), prior information about the importance of vaccination (adjusted odds ratio = 3.35, p = 0.004), previous hepatitis B testing (adjusted odds ratio = 3.14, p < 0.001), and fear of contracting hepatitis B (adjusted odds ratio = 2.39, p = 0.028) were independently associated with vaccine uptake.ConclusionHepatitis B virus vaccine uptake among medical students was significantly associated with vaccine awareness, perceived risk of infection, and prior hepatitis B testing, whereas scheduling conflicts, vaccine cost, and vaccine unavailability acted as barriers to vaccination. Strengthening awareness and addressing structural barriers are important for improving vaccination coverage.
Personalized vaccines provide the advantage of patient-specific antigen selection to optimize immune responses, a strategy extensively explored in oncology through neoantigen-targeted peptide, mRNA, and dendritic cell platforms. Peptide vaccines provide simplicity and stability though often elicit limited cytotoxic T-cell responses. What is more, mRNA vaccines lead to rapid, multiplexed neoantigen delivery, endogenous antigen processing and eventually improved immunogenic coverage. Dendritic cell-based vaccines have the potency to prime potent T-cells although this technology requires labor-intensive manufacturing and extensive production timelines. Integration with immune checkpoint inhibitors, adoptive cell therapies, and oncolytic viruses further enhances efficacy, suggesting that rational combinations may be more effective than single modalities. Recent advances in sequencing, computational epitope prediction, and bioinformatics pipelines have facilitated neoantigen prioritization and DC vaccine design, enabling more rapid and precise personalization. Hybrid vaccination strategies, such as ex-vivo mRNA-electroporated dendritic cells and in-vivo DC-targeted platforms, bridge the gap between manufacturing feasibility and potent immune activation. Emerging technologies, including AI-driven neoepitope prediction, receptor-targeted antigen delivery, biomaterial-based modulation, and distributed mRNA manufacturing, seem to be promising approaches to accelerate personalized vaccine development in future. From another point of view, lessons learned from the COVID-19 pandemic accelerated the development, large-scale deployment, and validation of mRNA vaccine platforms for infectious diseases. Host HLA diversity, prior immune history, and viral evolution create heterogeneity in immune responses, highlighting opportunities for semi-personalized or adaptive strategies. In this review, we provide a landscape of personalized vaccines, with a focus on DC-based platforms, and explore translational lessons for viral pathogens. A conceptual framework linking cancer immunotherapy and infectious disease preparedness is proposed, emphasizing hybrid personalization approaches, rapid manufacturing, and AI-enabled epitope selection. This perspective highlights how convergence of immunology, computational biology, and advanced vaccine technologies could expand the scope of personalized vaccination, from oncology to future epidemic and pandemic scenarios as well as the current challenges.
Objectives: A common inflammatory condition affecting oral health is periodontitis, which can lead to tooth loss if not treated early, as it destroys the supporting structures of the teeth. Fusobacterium nucleatum is an orange-pigmented bacterium commonly referred to as "the bridging species" between early and late colonizers in the oral microbiota, and it is associated with the progression of periodontal disease. This study aimed to develop an effective and precise multi-epitope vaccine against F. nucleatum, as there is currently no approved vaccine for periodontal disease. Materials and Methods: This study employed a computational method to design a multiple epitope-based vaccine against F. nucleatum using an immunoinformatics reverse vaccinology approach. FadA, a novel adhesin unique to F. nucleatum, was a suitable peptide for vaccine development. B- and T-cell epitopes were identified and assessed to design a multi-epitope vaccine. The developed vaccine construct was analyzed for potency based on its allergenicity, antigenicity, solubility, and stability. Results: The vaccine structure was non-allergenic and exhibited high antigenicity, stability, and solubility. This vaccine may be a candidate for eradicating F. nucleatum, based on predictions of immunogenicity responses. Conclusion: The designed vaccine construct could generate an effective immune response against F. nucleatum, owing to its high antigenicity and non-allergenicity.
The AS01E-adjuvanted respiratory syncytial virus prefusion F protein vaccine (adjuvanted RSVPreF3) received its first marketing authorization in May 2023 for the prevention of respiratory syncytial virus lower respiratory tract disease in individuals aged ≥ 60 years. We conducted a review of post-marketing safety surveillance data following adjuvanted RSVPreF3 administration. Spontaneous adverse events (AEs) that were reported worldwide since the first approval (3 May, 2023) to 2 May, 2025 in the GSK global safety database were analyzed. Up to 2 May, 2025, 13.4 million doses of adjuvanted RSVPreF3 were distributed globally. A total of 2861 spontaneous reports, including 7012 AEs (serious: 11.0%), were received. The most frequent AEs consisted mainly of non-serious reactogenic events. Of all reports, 1164 described vaccination errors, with most frequent errors consisting of either wrong product administration (N = 243) or administration to patients of an inappropriate age (N = 204). The majority (90.3%) of vaccination error reports were not associated with any other AEs. Adjuvanted RSVPreF3 was erroneously administered to pregnant individuals in 415 cases; most reports (95.2%) occurred without associated AEs. Observed-to-expected analysis of reports of Guillain-Barré syndrome (N = 37) did not suggest an increased risk compared to background incidence of this event and the reports of atrial fibrillation (N = 29) did not indicate an excess risk. Review of the post-marketing surveillance data from 2 years of exposure to adjuvanted RSVPreF3 showed that the safety profile of the vaccine is consistent with that observed in clinical trials supporting an unchanged and favorable benefit-risk profile for the vaccine. Additional post-marketing surveillance is ongoing to further evaluate a potential risk of rare AEs, such as Guillain-Barré syndrome, following adjuvanted RSVPreF3 vaccination. Respiratory syncytial virus is an important cause of severe lung infections in older adults. Adjuvanted RSVPreF3 vaccine was first approved in 2023 to prevent respiratory syncytial virus disease in adults aged 60 years and older. Regularly analyzing safety information from ongoing studies and real-world data (from routine healthcare practice) is essential to identify any potential new risks linked to adjuvanted RSVPreF3. Using the manufacturer’s (GSK) safety database, we analyzed the real-world safety data from individuals who experienced adverse events after vaccination with adjuvanted RSVPreF3. These data were collected during the first 2 years since the vaccine’s initial approval. The majority of adverse events reported to the manufacturer were mild and consistent with those reported in clinical trials. Most individuals who received the vaccine by mistake did not experience adverse events. The proportion of individuals who experienced Guillain–Barré syndrome after vaccination was within the range of background incidence rates of this disease in older adults. The reports of atrial fibrillation reflected the natural history of the disease for the older population. The safety data, collected over 2 years of substantial exposure to adjuvanted RSVPreF3, show that the safety profile of this vaccine is similar to that seen in clinical trials. Together with pre-licensure data demonstrating the vaccine’s ability to protect and help the immune system against respiratory syncytial virus disease, and real-world data demonstrating that adjuvanted RSVPreF3 protects against respiratory syncytial virus-associated hospitalization, the safety information collected so far supports the vaccine’s use for the people for whom it is authorized.
Internationally Educated Healthcare Professionals (IEHPs) represent a significant part of Canada's health workforce, yet limited evidence exists on vaccine attitudes in this group. This study examined vaccine perceptions among IEHPs in Canada and their roles in promoting vaccination within their communities. Semi-structured interviews were conducted with 22 IEHPs and analyzed using thematic analysis through an intersectional lens. Participants generally expressed strong pro-vaccine attitudes and believed that gender/sex, religion, ethnicity/race, and employment precarity, particularly in relation to vaccine mandates, influence vaccine attitudes, and decision-making. Participants viewed IEHPs as ambassadors who can promote vaccine uptake, especially among culturally and ethnically similar populations. IEHPs demonstrated overall support for vaccination and identified themselves as contributors to vaccine promotion in communities historically underserved by public health. These findings highlight their potential role in culturally tailored vaccine communication and public health outreach in Canada as well as in policy development and implementation efforts.
Vaccine hesitancy contributes to under-vaccination and recurring outbreaks of vaccine-preventable diseases in the United States. Rates are particularly low in rural areas. This qualitative study identified informational needs, trust in health information sources, and preferences for vaccine-related messaging to inform the design of a mobile application tailored to improve vaccine confidence and deliberative decision-making among rural caregivers. Parents or caregivers of children aged newborn to 3 years from Montana and Nebraska were recruited based on their level of childhood vaccination hesitancy using the Parent Attitudes About Childhood Vaccines (PACV) scale. Overall, 32 caregivers (18 fromF Montana, 14 from Nebraska), grouped by low (31%), medium (19%), and high (44%) hesitancy, participated in focus groups and follow-up individual interviews. Consensus coding and thematic analysis using NVivo software was used to identify key themes and patterns. Participants expressed key informational gaps, including questions about how vaccines work, safety testing, and the rigidity of immunization schedules. Gain-framed messages emphasizing benefits were consistently preferred over loss-framed messages, which were often perceived as judgmental or manipulative. Trust in local healthcare providers was a critical determinant of vaccine acceptance, surpassing trust in national health organizations. Participants advocated for non-judgmental, interactive, and personalized communication tools that mimic the relational trust found in provider interactions. Findings support vaccination communication strategies that integrate trusted local messengers, transparent and empowering framing, and participatory engagement. Insights directly inform the design of a parent-facing mHealth application customized according to preferences elicited from our diverse participant stakeholders.
Swine Group A rotavirus is one of the primary intestinal pathogens causing severe diarrhea in newborn piglets, with high incidence and mortality resulting in substantial economic losses to the global swine industry. Vaccination, alongside rigorous biosecurity measures, remains the core strategy for controlling porcine Group A rotavirus infection; however, continuous genetic variation via genomic reassortment, point mutations, and diverse G/P genotype combinations drives the constant emergence of new circulating strains that may evade immune protection from existing vaccines. These genetic changes may also give rise to highly pathogenic variants, increasing large-scale outbreak risk. Therefore, developing vaccines that provide stable, broad cross-protection against viral strain diversity is particularly critical. Vaccine adjuvants play a vital role in enhancing and modulating immune responses, broadening protection spectra, and reducing the antigen dose required for protection especially valuable when facing rapidly changing genotypes or limited vaccine antigen supplies. In recent years, advances in adjuvant design and formulation strategies have clearly improved the immunogenicity and duration of protection of swine Group A rotavirus vaccines, as evidenced by significantly reduced diarrhea incidence and viral shedding intensity in vaccinated piglets. Building on an overview of the current status, advantages, and challenges of different porcine Group A rotavirus vaccine types, this review focuses on the mechanisms of action, application advantages, existing limitations, and methodological strategies of adjuvants. It further analyzes the potential contribution of adjuvant strategies to developing a universal porcine rotavirus vaccine capable of broad, long-lasting cross-protection. Finally, this review identifies key unresolved scientific questions and critical knowledge gaps in the field, with the aim of guiding future research priorities.
COVID-19 pandemic caused significant mortality and morbidity locally and globally. Vaccines were introduced as the most effective medical countermeasure against severe morbidity, hospitalization, and death. However, vaccine uptake remains suboptimal in many countries in Sub-Saharan Africa. This study assessed uptake of COVID-19 vaccines and intention to vaccinate and associated factors in the Democratic Republic of the Congo. We carried out a cross-sectional survey with data collected from April to May 2022 through mobile phones in the DRC among 1075 persons. Uptake of COVID-19 vaccines and Intention to vaccinate were the main outcome variables. Of the participants, 89/1075 (8.3%) declared having received a full dose of the vaccine, and 38/1075 (3.4%) had received an incomplete dose. Results show that the uptake of the COVID-19 vaccine was associated with being older (adjusted PR = 1.87; 95% CI: 1.05-3.27), living outside of Kinshasa (adjusted PR = 1.77; 95% CI: 1.24-2.53), perceiving the Ministry of Health as competent with regard to the COVID-19 response (adjusted PR = 1.57; 95% CI: 1.05-2.35), and identifying health workers as a source of information for COVID-19 (adjusted PR = 1.62; 95% CI: 2.34). Seven out of 10 respondents declared the intention to be vaccinated. Being female (adjusted PR = 0.83; 95% CI: 0.75-0.92), having a high perception in the competence of the MOH staff on COVID-19 response (adjusted PR = 1.24; 95% CI: 1.13-1.36), and trusting radio as a source of information for COVID-19 (adjusted PR = 1.11; 95% CI: 1.02-1.22) were factors associated with the intention for COVID-19 vaccination. Biological factors (age and sex), perceiving the MOH as competent with regard to the COVID-19 and sources of COVID-19 information (radio and health workers) must be taken into account for the development of strategies to improve the uptake of these interventions for COVID-19 prevention and control.
Infections caused by multidrug-resistant (MDR) pathogens, both gram-negative and gram-positive organisms, have transformed into a silent global pandemic. These pathogens, especially ESKAPE pathogens, exhibit wide resistance patterns to several clinically significant antibiotics. This has decreased the effectiveness of already available antibiotics, increasing mortality, morbidity, economic burden and prolonged hospital stay. As the discovery of new antibiotics is an extensive and time-consuming process, an urgent need for innovative and practical preventive strategies arises. This review emphasizes the need, advancement and practicality of immunoinformatic tools and in silico vaccine designing and development against MDR pathogens. Research shows that MDR pathogens demonstrate a variety of resistance pathways, including target alteration, enzymatic degradation and efflux pumps, to tolerate therapeutically available antibiotics. The notable benefits of in silico vaccine designing include rapid identification of conserved antigens, even in variable pathogens, epitope prediction with antigenic potential, population coverage across various populations, less time, cost and improved precision in creating a multi-epitope vaccine against these MDR pathogens. Moreover, molecular docking, molecular dynamic simulations, immune simulations and expression analysis assist in predicting the molecular behavior of the designed vaccine. The increasing prevalence of MDR infections emphasizes the critical need for prevention measures rather than conventional therapy options. Use of immunoinformatics and in silico approaches presents a potent, efficient and cost-effective method to design and create multi-epitope vaccines against MDR pathogens. However, limitations such as false positives, reproducibility concerns with varying software and potential bias due to the use of curated databases in reverse vaccinology may pose a challenge. Incorporation of in silico vaccine development in future research can play a pivotal role in combating antimicrobial resistance and improving health outcomes globally.
The concurrent circulation of influenza viruses and SARS‑CoV‑2 continues to strain global public health systems. Vaccination remains the cornerstone of defense, and combined vaccines offer a strategic advantage by simplifying logistics, reducing costs, and improving coverage. In this set of studies, we evaluated the safety and immunogenicity of a novel combined quadrivalent influenza and recombinant COVID‑19 vaccine (developed by Anhui Zhifei Longcom Biopharmaceutical Co., Ltd.), known as the Flu‑CoV2 vaccine, in Sprague‑Dawley rats. Three independent studies were conducted in accordance with ICH S6(R1) guidelines for Preclinical Safety Evaluation of Biotechnology‑Derived Pharmaceuticals: primary immunization (Study 1) and booster immunization following a prior history of either influenza (Study 2) or COVID‑19 (Study 3) vaccination. Immunogenicity was determined by immunoglobulin G (IgG) antibody enzyme‑linked immunosorbent assay, plaque reduction neutralization tests for SARS‑CoV‑2, and hemagglutination inhibition assays for influenza viruses. No severe, life‑threatening, or fatal adverse reactions occurred during any of the studies. Transient injection‑site nodules in adjuvanted groups resolved completely, and all transient post‑vaccination shifts in hematologic and biochemical parameters normalized by the end of the recovery period. As a primary regimen, the Flu‑CoV2 vaccine effectively induced strong IgG and neutralizing antibody responses against both influenza and SARS‑CoV‑2. Administered as a booster, it markedly augmented specific antibody levels in pre‑immune models, demonstrating its potential to broadly enhance recall immune responses. These preclinical data demonstrate a favorable safety profile and potent immunogenicity, supporting the further development of the Flu‑CoV2 vaccine as a promising tool to address the dual threat of influenza and COVID‑19.
There is a pressing need to develop novel strategies to ameliorate symptoms and slow the progression of Alzheimer's disease. One of the hallmarks of Alzheimer's disease is the high levels of tau protein, which can form toxic oligomers and characteristic neurofibrillary tangles in the brain. Antitau antibodies can potentially bind tau protein and reduce tau pathology. In order to elicit a powerful antitau antibody response, virus-like-particle bacteriophage Qβ-based conjugate vaccines were developed targeting the microtubule binding region of tau protein. The Qβ-tau vaccines were able to produce a strong antitau antibody response in not only wild-type mice but also in human tau transgenic mice and a llama. The levels of antibody induced were superior to those generated by a corresponding keyhole limpet hemocyanin-based tau conjugate mimicking the one vaccine that successfully completed phase 1/2 human clinical trials. The Qβ-tau vaccine significantly improved the cognitive functions of the immunized mice and reduced the levels of inflammatory cytokines and tau in the brains, suggesting its translational potential.
Measles remains a major cause of child morbidity and mortality in low-resource settings. Young infants are particularly at risk of severe disease, with many lacking protective levels of maternal antibodies by six months. Vaccination before nine months in high-burden settings may confer earlier protection; however, concerns exist about its effectiveness at this age. We present early findings on enrolment, safety, and measles infections following the administration of a registered measles-containing vaccine at six months versus nine months (MR1) with a subsequent booster (MR2) at 12 or 18 months of age. We conducted an open-label randomised controlled non-inferiority trial at four health facilities in Kampala, Uganda. Infants aged 24-28 weeks were randomly assigned to receive MR at six and 12 months (group A), nine and 18 months (group B) or six and 18 months (group C). Infants were electronically randomised in a 1:1:1 ratio using block randomisation of varying sizes, stratified by site, maternal HIV status and baseline haemoglobin level. Caretakers recorded solicited reactions on paper diary cards, with safety-related events evaluated. 450 infants received MR1 and were enrolled. No differences in local or systemic post-vaccination events between the six and nine months MR1 groups were observed [Local: 21·2% versus 21·9% (p = 0·959), systemic: 29·2% vs. 27·7% (p = 0·845)]. Most local reactions were mild and within the first four days. The majority (5/6) of hospitalisations followed common childhood illnesses, with one non-vaccine-related death six months post-MR1. Sixteen laboratory-confirmed cases of measles (10) and rubella (6), and three clinical measles cases before MR1 were registered. Most measles cases (70·0%) occurred in group C, with no measles cases registered two weeks post-MR2. We provide further evidence on the safety of administering a measles-containing vaccine at six months of age.Trial registration: The trial was registered on 31st October 2024 with Clinicaltrials.gov with the identifier NCT06667206. The online version contains supplementary material available at 10.1007/s44337-026-00649-x.
DNA vaccines are a promising against avian coccidiosis but they require comprehensive safety evaluation before clinical application. This study assessed the safety and environmental impact of pVAX-ROP27 DNA vaccine against Eimeria tenella in both chickens and mice. Chickens received intramuscular immunizations: single low dose at 1 day (100 μg), repeated doses (100 μg at 7, 14, 21 days), or a high dose (300 μg at 14 days) using three vaccine batches. Mice received a single dose or overdose. Clinical signs, body weight, and histopathology were evaluated. Distribution and persistence of EtROP27 and Kana genes in tissues, faeces, and water were detected by PCR. No adverse reactions or significant weight differences were observed (P > 0.05). Both genes were detected in all tested tissues (heart, liver, spleen, lung, kidney, blood, small intestine, testis, injection site muscle) at 0.5 months but became undetectable by 2 months, suggesting clearance within the detection limit of conventional PCR, with no evidence of genomic integration by this method. No histopathological lesions or environmental gene release (in faeces/water up to 8 weeks) were detected, confirming a favorable safety profile with no detectable tissue damage, integration, or environmental spread within the observation period.
Therapy-related acute myeloid leukemia often exhibits adverse biologic features and treatment resistance. Allogeneic hematopoietic stem cell transplant as consolidation in remission status after initial therapy offers the greatest possibility of long-term disease control. For patients without options of human leukocyte antigen-matched family donor or unrelated human leukocyte antigen-matched donor or killer immunoglobulin-like receptor-favorable haploidentical donor, an alternative strategy using vaccine hematopoietic stem cell transplant such as complementary haplo-cord hematopoietic stem cell transplant could have good graft-versus-leukemia effect and enable long-term remission. Here, we reported a successful case of more than 3 years of leukemia-free survival in a patient with therapy-related acute myeloid leukemia who underwent haplo-cord hematopoietic stem cell transplant with vaccine effect.
Malignant melanoma is an aggressive skin cancer with limited responsiveness to traditional therapies. Notably, the combination of dendritic cell (DC) vaccines with anti-programmed cell death protein 1 (anti-PD-1) therapy has shown stronger clinical potential than conventional approaches. Understanding the tumor-immune interplay is essential for optimizing melanoma immunotherapy strategies. In this paper, we formulate a melanoma-specific tumor-immune interaction model of tumor cells (TCs), DCs, and effector CD8+ T cells (ECs). A key threshold value is identified to characterize tumor growth. Using this threshold, we determine the conditions for tumor-free and tumorous equilibria, consistent with cancer immunoediting theory. Furthermore, bifurcation analysis indicates that the model exhibits oscillatory behavior under certain conditions. Sensitivity and parameter heterogeneity analyses reveal that tumor burden is mainly regulated by the intrinsic tumor growth and immune activation rate. Moreover, to better reflect physiological realism, we extend the model to a time-delayed system by incorporating a constant delay for DC-to-EC activation. Analytical and numerical results demonstrate a supercritical Hopf bifurcation at a critical delay τ0 ≈ 4.68 days, leading to stable periodic solutions. Finally, an optimal control framework is proposed to design DC vaccines and anti-PD-1 injection protocols. Compared with the constant dosing strategy, optimal control achieves enhanced tumor suppression for the same total treatment intensity. This work elucidates the dynamical mechanisms of melanoma-immune interactions and establishes a theoretical foundation for personalized combination immunotherapies.
The COVID-19 pandemic was a significant global mortality shock. In addition to baseline differences in mortality risk, males often face a survival disadvantage in crisis situations such as famines and epidemics. Although many countries have reported higher numbers of male COVID-19 deaths, the evolution of sex differences in mortality over the course of the pandemic, and how these differences compare using both relative (accounting for higher male baseline mortality) and absolute measures remains underexplored. This study aimed to assess absolute and relative sex differences in all-cause excess mortality during the COVID-19 pandemic across three pandemic phases in 34 high-income countries. We examined sex differences in excess mortality from February 2020 to July 2023 using data from 34 countries in the Short-Term Mortality Fluctuations dataset. We estimate both absolute (male excess mortality-female excess mortality) and relative (male P-score-female P-score) sex differences in pandemic-related all-cause excess mortality. We analysed sex differences monthly and across three pandemic phases: pre-vaccine, post-vaccine, and endemic. In most countries, absolute male excess mortality exceeded that of females during the pre-vaccine phase of the pandemic. A significant absolute male disadvantage in excess mortality rates was observed in 60% (81/136) of age-group-country combinations in the pre-vaccine phase, decreasing to 51% (70/136) in the post-vaccine phase and 23% (31/136) in the endemic phase. In contrast, a male disadvantage was less common for relative changes: a significant male disadvantage in excess mortality P-scores was observed in only 28% (38/136) of age-group-country combinations in the pre-vaccine phase and 14% (19/136) in the post-vaccine phase. The remaining combinations showed either no significant sex difference or a female disadvantage, with little evidence of relative sex differences during the endemic period. Sex differences in absolute excess mortality tended to grow with age, but there was no clear pattern in the relative sex differences across age groups. While previous research has highlighted a male disadvantage in COVID-19 mortality based on absolute death counts, our study shows that this pattern was concentrated in the pre-vaccine phase and declined over time. Relative increases in all-cause excess mortality were often similar between sexes and, in some cases, greater among women. These findings suggest that sex differences in pandemic-related mortality were more varied than commonly assumed and underscore the importance of using both absolute and relative measures to assess the impact of health crises on population subgroups. Finally, our results suggest that COVID-19 did not produce lasting shifts in sex differences in mortality. This work was supported by the European Research Council (ERC-2021-CoG-101002587) and the Leverhulme Trust (Grant RC-2018-003) for the Leverhulme Centre for Demographic Science.
Recently, a respiratory syncytial virus (RSV) vaccine was approved and recommended for pregnant women in Saudi Arabia. Data are needed regarding pregnant women's awareness of RSV infection and their acceptance of the RSV vaccine. Therefore, in this study, we aimed to assess the awareness and acceptance of antenatal RSV vaccines among postpartum women in Al-Madinah, Saudi Arabia. This hospital-based, cross-sectional study was conducted at two hospitals in Al-Madinah, Saudi Arabia. A validated 13-item questionnaire was used, including questions regarding demographic data, awareness of RSV infection, and acceptance of the antenatal RSV vaccine. Multivariate binary logistic regression analysis was used to assess the association between demographic data and awareness and acceptance of the antenatal RSV vaccine. Among 400 postpartum women (mean age, 30 years; range, 18-44 years), 51% were aware of RSV infection. Most provided correct answers regarding the mode of RSV transmission (72.5%). Approximately 40% of the participants perceived the seriousness of the RSV infection to be high for infants after delivery. Acceptance for receiving the RSV vaccine was moderate (58%). Compared with high school or lower educational level, university or higher education was associated with lower acceptance of the RSV vaccine (odds ratio, 0.72; 95% confidence interval, 0.56-0.93). Despite moderate awareness of RSV infection, maternal acceptance of the antenatal RSV vaccine among highly educated women was lower than that among women with a lower education level. This low acceptance rate highlights the need for future studies to evaluate the actual uptake of antenatal RSV vaccination among highly educated women.
Vaccinations are widely recognized for protecting children from infectious diseases. During the COVID-19 pandemic, immunization efforts became especially important. Despite these efforts, achieving high vaccine uptake has remained challenging in Uganda, underscoring the need to better understand the factors that influence caregivers' decisions regarding childhood COVID‑19 vaccination. The acceptability of routine childhood COVID-19 vaccine boosters among parents or caregivers in Uganda remains uncertain. This study examined factors associated with parent/caregiver willingness to vaccinate their children against COVID-19 in an urban immunization clinic in Kampala, Uganda. We conducted a cross-sectional study among 230 caregivers with children under 59 months of age in an urban postnatal clinic in Kawempe Division, Kampala, Uganda, from June 2023 to July 2023. The outcome was willingness to receive annual routine COVID-19 vaccination for their child. Covariate selection was informed by the World Health Organization (WHO) Behavioral and Social Drivers (BeSD) framework: (i) thoughts and feelings (disease risk perception, confidence in vaccine safety, and benefits), (ii) social processes (family and friend norms), and (iii) practical issues (affordability). Modified Poisson regression identified factors independently associated with willingness to receive routine COVID-19 vaccination for their children. Adjusted prevalence rate ratios (adj. PRR) and 95% confidence intervals (95% CI) were calculated. P-values of <0.05 were considered statistically significant. Among 230 respondents, 83.9% (n = 193) reported willingness to vaccinate their children against COVID-19, with female caregivers aged 15-24 years comprising 51% (n = 117) of our study sample. After controlling for confounders, willingness was higher among those with moderate confidence in vaccine benefits (PRR: 3.07; 95% CI: 1.37-6.85; p = 0.006) and very important confidence in vaccine benefits (PRR: 3.11; 95% CI: 1.41-6.89; p = 0.005), positive family norms (PRR: 1.35; 95% CI: 1.04-1.75; p = 0.022), and intention to vaccinate themselves (PRR: 2.68; 95% CI: 1.18-6.07; p = 0.019). Targeting BeSD factors related to confidence in vaccine benefits, family norms, and parent/caregivers' vaccination intentions could help address barriers to routine childhood COVID-19 vaccination, potentially improving COVID-19 vaccination rates among urban, healthcare-seeking caregivers in similar study settings.
Respiratory mucosal (RM) immunity is a highly specialized and dynamic network that safeguards the airways from inhaled pathogens while preserving tissue homeostasis. Acting as the body's first line of defense, RM immunity integrates immune tolerance, barrier protection, immune surveillance, tissue repair, and the establishment of long-term immunological memory. Dysregulation of these processes contributes to a broad spectrum of diseases, including acute viral and bacterial infections, fungal colonization, and chronic inflammatory disorders, highlighting the urgent need for effective preventive strategies targeting the respiratory mucosa. The unprecedented global impact of coronavirus disease 2019 (COVID-19) has further highlighted this need and catalyzed rapid advances in vaccines capable of inducing both local and systemic immunity at the respiratory portal of entry, alongside progress in inhalable antibody therapies. This review first summarizes the principal biological functions of the respiratory mucosa and the underlying mechanisms, followed by an overview of immune dysregulation associated with respiratory diseases. It then highlights recent advances in mucosal intervention strategies, with a particular focus on the development of RM vaccine platforms-including live-attenuated, inactivated, viral vector, protein subunit, and mRNA vaccines. It further discusses next-generation RM vaccine strategies emphasizing upper airway immunity, broadened antigen design and intranasal safety. Together, these advances provide a conceptual and translational framework for advancing RM-based interventions against respiratory pathogens.