As this Special Issue concludes, we are delighted to highlight the diversity, depth, and translational potential of the assembled contributions [...].
As this Special Issue concludes, we are delighted to highlight the diversity, depth, and translational potential of the assembled contributions [...].
There was an error in the original publication [...].
Background: Hepatitis B vaccination is the most effective strategy for preventing chronic hepatitis B virus (HBV) infection; however, interindividual variability in vaccine-induced antibody responses remains a significant challenge in the field. Innate immune components, particularly lectin complement pathway proteins such as mannose-binding lectin (MBL), mannose-associated serine protease 1 (MASP-1), and mannose-associated serine protease 2 (MASP-2), may contribute to this variability in outcomes. This study aimed to evaluate the association between serum MBL, MASP-1, and MASP-2 levels, birth weight, and humoral response to hepatitis B vaccination in infants. Methods: This single-center prospective observational study included 37 term infants who received hepatitis B vaccinations at birth, 1 month, and 6 months of age according to the national immunization schedule. Venous blood samples were collected at month 6, before, and month 7 after the 3rd vaccine dose. Serum MBL, MASP-1, MASP-2, and antiHB levels were measured using commercial ELISA and chemiluminescence assays. Data were analyzed using non-parametric statistical tests and Spearman's correlation analysis. Results: AntiHB levels increased significantly following vaccination (median Pre-3rdVac: 125.8 mIU/mL; Post-3rdVac: 609.7 mIU/mL; p < 0.001). MASP-1 concentrations also showed a significant Post-3rdVac increase (median Pre-3rdVac: 809.52 ng/mL; Post-3rdVac: 1133.93 ng/mL; p = 0.019). Birth weight was positively correlated with both MASP-1 levels (rs = 0.492, p = 0.004) and changes in MASP-1 concentrations (rs = 0.524, p = 0.002) after the third dose. In addition, MASP-1 levels were positively associated with antiHB levels (rs = 0.385, p = 0.030) and Post-3rdVac antiHB titers (rs = 0.493, p = 0.004). In contrast, serum MBL and MASP-2 concentrations were not significantly associated with antiHB levels before or after vaccination. Conclusions: MASP-1, but not MBL or MASP-2, is associated with the magnitude of the antibody response to hepatitis B vaccination in infants. These findings suggest that specific components of the lectin pathway may influence vaccine-induced immunity, independent of MBL. Further large-scale studies incorporating genetic and functional analyses are warranted to clarify the mechanisms by which lectin pathway proteins shape hepatitis B vaccine response.
Background: On 1 January 2019, a 2-dose mumps-containing vaccine (MuCV) immunization strategy was adopted in Henan Province before the national Expanded Program on Immunization (EPI). This study examines the epidemiological characteristics of mumps cases during the implementation of various immunization strategies in Henan Province.
Methods: We employed descriptive statistics and initially retrieved data on reported cases from 2004 to 2024. Mumps case data were sourced from the China Information System for Disease Control and Prevention (CISDCP).
Results: Between 2004 and 2024, a total of 301,342 cases of mumps disease were reported in Henan Province, and the average annual reported incidence was 15.11 cases per 100,000 people. The average yearly incidence decreased by 60.29% following the implementation of the 2-dose vaccination strategy compared with the one-dose strategy. The study identifies two annual incidence peaks from 2004 to 2024: a prominent peak from April to July and a smaller peak from December to January. From 2019 to 2024, in addition to a slight dip in February, the seasonality was less pronounced, with cases distributed sporadically throughout the year. The proportion of the population over 20 years old increased annually, from 8.17% in 2004-2008 to 15.55% in 2019-2024. There was an overall negative correlation between the estimated MuCV vaccination rate and the reported incidence of mumps (r = -0.685, p < 0.05).
Conclusions: The introduction of 2-dose MuCV in the EPI significantly reduced the incidence rate and total number of cases. While continuing the 2-dose MuCV immunization strategy in the future, it is crucial to remain vigilant in preventing and controlling mumps among individuals over 20 years old.
Background/objectives: Respiratory Syncytial Virus (RSV) causes severe disease in infants, the elderly, and immunocompromised individuals, with reinfections linked to poor induction of durable mucosal immunoglobulin A (IgA). We investigated the role of IgA in immunity and protection induced by a RSV subunit vaccine candidate, tFrsc/TriAdj, which consists of a truncated RSV fusion protein (tFrsc) with a tri-component adjuvant (TriAdj).
Methods: Wild-type (IgA+/+) and IgA-deficient (IgA-/-) BALB/c mice were immunized intranasally and subsequently challenged with RSV.
Results: Vaccination with tFrsc/TriAdj induced robust systemic and mucosal IgG, and high lung and serum neutralizing antibodies, in both IgA+/+ and IgA-/- mice. As expected, IgA-/- mice lacked IgA and exhibited modest reductions in nasal IgG compared to IgA+/+ mice following challenge, correlating to failure to clear RSV from the upper respiratory tract. In contrast, viral replication in the lungs was fully suppressed in both genotypes, indicating that IgG alone was sufficient for lower respiratory tract protection. Isotype analysis revealed diminished Th1-associated IgG2a and elevated IgG1 across mucosal and systemic compartments in IgA-/- mice, suggesting a Th2 bias. Flow cytometric analysis confirmed reduced recruitment of IFN-γ+ CD4+ T cells in the lungs of immunized IgA-/- mice. Interestingly, IL-17 production and numbers of IL-17+ CD4+ T cells in the lungs were increased, suggesting an enhanced Th17 response. Furthermore, IgA-deficient mice displayed reduced splenic IgG+ B cell populations, which is also a novel observation.
Conclusions: Collectively, these findings demonstrate that although tFrsc/TriAdj confers lower airway protection in the absence of IgA, vaccine-induced IgA is critical for upper airway protection, Th1/balanced immune responses, and optimal B cell responses.
Background/Objectives: Inadequate characterization of protective antigens poses a significant challenge to the development of vaccines for African swine fever (ASF), particularly for antigen-dependent formulations such as subunit, mRNA, and recombinant viral vector vaccines. To address this, we aimed to screen African swine fever virus (ASFV) antigens and enhance their immunogenicity using a nanoparticle delivery platform. Methods: Here, six ASFV antigens (p30, p54, pE120R, pH124R, pE184L, and CD2v) were purified and used to immunize pigs individually. The effects of antibodies induced by these six antigens on ASFV replication or hemadsorption was evaluated in primary porcine alveolar macrophages (PAMs). These six antigens were, respectively, conjugated to ferritin via SpyTag/SpyCatcher to prepare six ferritin nanoparticles. A cocktail of the six mixed antigens or a cocktail of the six mixed nanoparticles was used to immunize pigs separately, and the differences in induced humoral and cellular immune responses were compared. Results: Antibodies generated against p30, p54, pE120R, pH124R, and pE184L in immunized pigs significantly inhibited ASFV replication in PAMs, while anti-CD2v antibodies specifically obstructed the hemadsorption of ASFV. Notably, immunization with a cocktail of these antigen-conjugated nanoparticles elicited a stronger virus-inhibitory antibody response compared to immunization with a cocktail of antigen monomers. Furthermore, nanoparticle immunization induced robust cellular immunity, evidenced by elevated serum IFN-γ, increased numbers of ASFV-specific IFN-γ-secreting cells, and an expanded CD8+ T cell population. Conclusions: Our study identifies a set of promising ASFV antigen candidates and demonstrates that ferritin nanoparticle delivery synergistically enhances both humoral and cellular immune responses against ASFV, providing a rational strategy for multi-antigen ASF vaccine design.
Background: Administering several separate childhood vaccines can reduce adherence to immunization schedules due to missed appointments and the burden of repeated injections. A hexavalent formulation targeting diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type B, and poliovirus offers a practical approach to improve compliance and streamline immunization.
Methods: Toxicity testing was performed in Wistar rats and New Zealand White rabbits (60 rats and 30 rabbits). Animals were distributed into three groups: hexavalent vaccine + low-dose sIPV, hexavalent vaccine + high-dose sIPV, and control. Each animal received a 0.5 mL intramuscular injection at weeks 0, 4, 8, and 12. Clinical observations were conducted throughout the study. Serum samples were collected one day before each injection and at the endpoint, while liver tissue was collected at the endpoint. ALT and AST concentrations were analyzed using an automated analyzer, and hepatic morphology was evaluated microscopically.
Results: No abnormal clinical signs related to vaccination were observed. ALT concentrations showed no significant differences (p > 0.05). AST differences (p < 0.05) were detected between the high-dose group and the control on day 27 in female rabbits and on day 83 in female rats; however, all values remained within normal physiological limits. Histopathological examination revealed no irreversible hepatic lesions, including hydropic degeneration, portal inflammation, focal necrosis, or connective tissue proliferation, and no significant differences were noted (p > 0.05).
Conclusions: Repeated administration of the hexavalent vaccine candidate at low and high doses produced no toxicological effects in animal models, supporting its safety for further clinical development.
Background: Men who have sex with men (MSM) using HIV pre-exposure prophylaxis (PrEP) experience a high burden of human papillomavirus (HPV) infection and related diseases, yet data on HPV vaccination among this group in Brazil remain limited. Aims: The aims of this study were to estimate the prevalence of complete HPV vaccination and to identify factors associated with vaccination completion among MSM using PrEP in Brazil. Methods: We conducted a cross-sectional online survey between May and September 2025 among MSM aged ≥18 years, residing in Brazil and currently using oral PrEP. Participants were recruited through virtual snowball sampling and targeted advertisements on social media and a gay geosocial networking application. Data were collected using a structured, self-administered questionnaire hosted on REDCap®. Complete HPV vaccination was defined as self-reported receipt of all doses recommended according to the participant's age and clinical condition. Sociodemographic characteristics, relationship patterns, sexual behaviors, lubricant use during sexual activity, and history of sexually transmitted infections (STIs) were assessed. Adjusted prevalence ratios (aPRs) and 95% confidence intervals (95% CIs) were estimated using Poisson regression with robust (sandwich) variance. Results: A total of 872 MSM using PrEP were included, of whom 59.4% reported complete HPV vaccination. In adjusted analyses, complete vaccination was more frequent among participants reporting both steady and casual partners (aPR = 1.90; 95% CI: 1.36-2.65) or only casual partners (aPR = 1.72; 95% CI: 1.24-2.39), those reporting lubricant use during sexual activity (aPR = 1.41; 95% CI: 1.23-1.61), and those with a diagnosis of chlamydia and/or gonorrhea in the previous 12 months (aPR = 1.22; 95% CI: 1.08-1.36). Conclusions: Although HPV vaccination coverage among MSM using PrEP in Brazil is higher than that reported for MSM in general, it remains incomplete in a population with regular contact with specialized health services. Integrating systematic assessment and delivery of HPV vaccination into PrEP care may help increase vaccination completion and reduce missed opportunities for prevention.
Background: Hand, foot, and mouth disease (HFMD) remains a major public-health concern in China. While the monovalent EV-A71 vaccine has effectively reduced EV-A71-associated cases, it offers no protection against CV-A16. The introduction of a bivalent EV-A71/CV-A16 vaccine may offer broader protection, but its economic viability under different immunization strategies remains uncertain.
Methods: We developed a dynamic transmission model integrated with cost-effectiveness analysis to assess the epidemiological and economic impact of a hypothetical bivalent EV-A71/CV-A16 vaccine in China. Based on the immunization program policy, seven vaccination strategies, vaccine effectiveness (VE) levels ranging from 50-95% against EV-A71/CV-A16, and coverage levels from 0-95% were evaluated. The threshold vaccine price (TVP) was derived based on incremental cost-effectiveness ratio (ICER) calculations. Cost-effectiveness was assessed using willingness-to-pay (WTP) thresholds defined as 1-3 times the gross domestic product (GDP) per capita.
Results: The mean cost of two doses of the monovalent EV-A71 vaccine was USD133.0 (95% CI: 126.9-139.1). Strategy 2, which targeted individuals unvaccinated with the monovalent EV-A71 vaccine, demonstrated the most favorable cost-effectiveness. At 45% coverage and 85% vaccine effectiveness, the estimated threshold price per dose was USD 107.7 (95% CI: 103.4-112.0), with threshold vaccine prices increasing as coverage declined. When vaccination coverage exceeded 80%, the threshold vaccine price decreased substantially, falling below USD 45.9 (95% CI: 43.5-48.3) per dose.
Conclusions: Large-scale inclusion in the national immunization program may not be economically justified at current cost levels. Targeted voluntary vaccination of unvaccinated, susceptible populations represents a more cost-effective and practical strategy during the early stage of vaccine introduction.
Background: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in the elderly. While pneumococcal vaccination is a core preventive measure, it remains unclear whether its association with severe CAP is uniform across all elderly subgroups. Our study aimed to evaluate the overall association of pneumococcal vaccination with the risk of severe CAP in hospitalized patients aged ≥ 65 years and to explore potential heterogeneity in this association using a causal forest model. Methods: We conducted a retrospective cohort study of patients discharged between January 2023 and June 2025, aged ≥ 65 years, with a primary diagnosis of CAP. We used multivariable logistic regression to estimate the average association and a causal forest model to explore heterogeneous patterns in the conditional average treatment effect (CATE). Results: Among 1906 included patients (severe CAP: 924; non-severe CAP: 982), PPSV23 vaccination was independently associated with reduced odds of all-cause severe CAP (adjusted OR = 0.610, 95% CI: 0.401-0.930). The causal forest model yielded an average treatment effect (ATE) estimate of -0.112 (95% CI: -0.200 to -0.023), corresponding to an 11.2 percentage-point reduction in absolute risk. Exploratory analysis suggested potential heterogeneity: the association appeared most pronounced in patients aged 65-74 years (CATE = -0.122) and showed an attenuating trend in older groups. Age was the primary variable associated with heterogeneity, followed by hypertension, SARS-CoV-2 infection, and sex. Conclusions: In this observational cohort study, PPSV23 vaccination was associated with a reduced risk of severe CAP in elderly inpatients under strong assumptions of no unmeasured confounding. Exploratory analyses suggested potential heterogeneity in this association, which appeared to attenuate with advancing age and may be influenced by comorbidities. These hypothesis-generating findings indicate that further investigation is needed to determine whether prevention strategies should be tailored for the very old and those with specific chronic conditions.

