Search Results (282)

Background and Objectives: Healthcare workers are at heightened risk of SARS-CoV-2 infection. Understanding the duration and protective value of vaccine-induced immunity is critical to inform booster strategies. This study investigates longitudinal dynamics of anti-SARS-CoV-2 receptor-binding domain IgG (anti-RBD IgG) antibodies and their association with infection risk among vaccinated healthcare workers. Materials and Methods: A prospective cohort study was conducted at Vilnius University Hospital Santaros Klinikos, Lithuania. A total of 1778 healthcare workers who completed a primary COVID-19 vaccination series were followed. Blood samples were collected every three months to measure anti-RBD IgG levels. Participants also received up to three booster doses. COVID-19 was identified by PCR, antigen tests, or positive anti-nucleocapsid IgG. For serologically detected cases, infection timing was assigned to the interval between study visits. Antibody dynamics were analyzed across vaccination stages, time, age groups, and circulating SARS-CoV-2 variants. Results: Anti-RBD IgG titers peaked in the first quarter after primary vaccination (mean 7904 AU/mL), declined sharply by quarters 2–3, and rose substantially after booster doses. Following the first booster, titers increased to ~12,598 AU/mL in quarter 1 and continued rising through quarter 3. The highest levels were observed after the second booster (24,456 AU/mL in Q1), followed by gradual decline. A high-titer plateau persisted from quarters 6 to 9 (~21,000 AU/mL), followed by decline in quarters 10–11 and partial rebound in Q12. Approximately 49.6% of participants experienced COVID-19 during follow-up. Antibody response patterns were similar across age groups, with only minor transient differences. Conclusions: COVID-19 booster doses significantly enhance and prolong humoral immunity in healthcare workers compared with the primary vaccination series. However, antibody waning over time emphasizes the need for timely boosters, particularly during periods of variant circulation. These findings support continued booster vaccination and monitoring of long-term immune protection, although anti-RBD IgG should be interpreted as a surrogate marker of humoral rather than overall immunity. Full article

The purpose of this project was to define gene expression changes associated with the acquisition and loss of resilience to diabetic retinopathy (RDR) in individual retinal cell types. A non-immune form of type 1 diabetes mellitus (DM) was induced by injecting male C57Bl6J mice with streptozotocin. Single-cell RNA sequencing was performed on retinas from mice that experienced DM for 5 or 15 days, along with retinas from age-matched, non-DM mice. The resulting data sets were analyzed to identify DM-associated differentially expressed genes and pathway enrichments after each duration of DM. We observed that acquisition of RDR, previously shown to arise after 5 days of DM was linked to altered expression of genes in a subset of retinal cells, mainly Müller cells. Pathway analysis indicated enhancement of numerous modes of protection, including reinforced neurovascular and structural homeostasis through phagocytosis, integrin signaling, and interferon-mediated defense. After 15 days of DM, when we previously showed that RDR is waning this pro-protection surge in gene expression subsided. We conclude that a duration of DM that is too short to cause diabetic retinopathy (DR) nonetheless evoked a profound change in the gene expression profile within a subset of retinal cell types. The nature and timing of this molecular shift indicated that it was not the preamble to DM-related damage that eventually develops. Rather, DM engaged numerous defense programs within Müller cells. The temporal alignment between RDR and activation of Müller cell-based defense provides a molecular foundation for the retina’s transient ability to remain healthy in the face of DM. Full article

This paper presents a unified analytical and computational framework for the study of typhoid fever transmission dynamics governed by a Caputo fractional-order compartmental model of order $\kappa \in (0,1]$. The population is stratified into five epidemiological classes, namely susceptible $\left(\mathcal{S}\right)$, asymptomatic $\left(\mathcal{A}\right)$, symptomatic $\left(\mathcal{I}\right)$, hospitalised $\left(\mathcal{H}\right)$, and recovered $\left(\mathcal{R}\right)$, and the governing system explicitly incorporates asymptomatic transmission, treatment dynamics, and temporary immunity with waning. The use of the Caputo fractional derivative is motivated by the well-documented existence of chronic asymptomatic Salmonella Typhi carriers, whose heavy-tailed sojourn times in the carrier state are naturally encoded by the Mittag–Leffler waiting-time distribution arising from the fractional operator. A complete qualitative analysis of the fractional system is carried out: the basic reproduction number ${\mathcal{R}}_0$ is derived via the next-generation matrix method; local and global asymptotic stability of both the disease-free equilibrium ${\mathcal{E}}_0$ (when ${\mathcal{R}}_0\le 1$) and the endemic equilibrium ${\mathcal{E}}^{*}$ (when ${\mathcal{R}}_0>1$) are established using fractional Lyapunov theory and the LaSalle invariance principle; and the normalised sensitivity indices of ${\mathcal{R}}_0$ are computed to identify transmission-amplifying and transmission-suppressing parameters. Existence, uniqueness, and Ulam–Hyers stability of solutions are established via Banach and Leray–Schauder fixed-point arguments. To complement the analytical results, a fractional physics-informed neural network ($\mathcal{PINN}$) framework is developed to simultaneously reconstruct compartmental trajectories and identify unknown biological parameters from sparse synthetic observations. $\mathcal{PINN}$ embeds the L1-Caputo discretisation directly into the training residuals and employs a four-stage Adam–L-BFGS optimisation strategy to recover five trainable parameters $\mathbf{\Theta }$ = $\{\varphi ,\mu ,\sigma ,\psi ,\beta \}$ across three fractional orders $\kappa \in \{1.0,0.95,0.9\}$. The estimated parameters show strong agreement with the true values at the classical limit $\kappa =1.0$ ($\mathrm{MAPE}=2.27\%$), with the natural mortality rate $\mu$ recovered with $\mathrm{APE}\le 0.51\%$ and the transmission rate $\beta$ with $\mathrm{APE}\le 3.63\%$ across all fractional orders, confirming the structural identifiability of the model. Pairwise correlation analysis of the learned parameters establishes the absence of equifinality, validating that $\beta$ can be reliably included in the trainable set. Noise robustness experiments under Gaussian perturbations of $1\%$, $3\%$, and $5\%$ demonstrate graceful degradation ($\mathrm{MAPE}$: $0.82\%\to 3.10\%\to 7.31\%$), confirming the reliability of the proposed framework under realistic observational conditions. Full article

Background: Sustaining measles elimination in the post-elimination era presents increasing challenges due to global resurgence and waning vaccine-induced immunity. We aimed to evaluate epidemiological trends, vaccination strategies, and population immunity associated with achieving and maintaining measles elimination in Taiwan. Methods: We conducted a comprehensive analysis of national surveillance data from 1991 to 2024, including case notifications, viral genotypes, vaccination coverage rates, and surveillance performance indicators. Three population-based seroprevalence surveys conducted between 2002 and 2020 were reviewed to assess age-specific immunity. Descriptive analyses were performed to characterize long-term epidemiological and immunological trends. Results: From 1993 to 2024, the annual number of measles cases remained consistently below 50, except in 2019. Vaccination coverage for both MMR1 and MMR2 has exceeded 95% since 1998, with MMR1 coverage remaining above 97% between 2009 and 2024. Genotyping evidence confirms the interruption of endemic transmission since 2006; furthermore, as of 2024, no continuous chains of transmission lasting longer than 12 months have been recorded. National seroprevalence surveys monitoring measles-specific IgG antibodies revealed declining antibody levels among adolescents and young adults, with seropositivity as low as 36.7% in specific cohorts. Despite this, transmission following importations has remained limited, with minimal secondary spread. Conclusions: Taiwan has successfully sustained measles elimination through high vaccination coverage, robust surveillance, and targeted interventions. Although serological evidence indicates waning immunity, epidemiological data suggest preserved population-level protection, likely mediated by immunological memory. Targeted booster strategies for high-risk groups may be more appropriate than universal additional dosing in post-elimination settings. Full article

Background: Since China incorporated the hepatitis B vaccine into its Expanded Program on Immunization (EPI) in 2002, the first cohort of infants to receive the full vaccination series has now reached college age. As vaccine-induced antibodies gradually wane, this cohort faces a higher risk of infection. Therefore, we assessed their current seroprotection status and evaluated the immunogenicity and short-term antibody kinetics of a single 60 μg booster dose in susceptible individuals, while also constructing a model of expected duration of protection. Methods: In a multicenter study across three Anhui universities, 2988 students were screened for HBV markers. Among them, 160 who tested negative for all five markers received a single 60 μg booster. Antibody titers were monitored for 1–5 months. Results: Serological screening showed 0.33% HBsAg positivity, 36.28% anti-HBs positivity, and 63.02% negativity for all markers, indicating high susceptibility. After the booster, seroprotection rate (SPR) remained >85% throughout follow-up, and anti-HBs geometric mean concentration (GMC) peaked at 1–2 months. Stratified analysis based on immune response status revealed that the proportion of high responders (≥100 mIU/mL) peaked early and then gradually declined, whereas the proportion of low responders (10–99.99 mIU/mL) increased over the follow-up period. A linear mixed-effects model predicted that protective levels (anti-HBs ≥10 mIU/mL) would persist for an average of 32.8 months. Conclusions: A substantial proportion of university students lack protective immunity against hepatitis B. A single 60 μg booster rapidly and effectively induced protection, demonstrating strong immunogenicity. These findings support implementing efficient booster strategies in university settings. Full article

Background: Hemodialysis patients are particularly vulnerable to hepatitis B virus (HBV) due to immunosuppression and repeated vascular access. While universal childhood vaccination has reduced population-level HBV prevalence, dialysis units require tailored prevention and monitoring strategies. This study aimed to characterize HBV serologic profiles, evaluate immune responses, and assess the kinetics of antibody waning in a diverse hemodialysis population. Methods: We retrospectively analyzed 565 adult hemodialysis patients (2015–2024), assessing HBV seroprevalence, seroconversion, booster response, and antibody waning. Subgroup comparisons were made by ethnicity and birth cohort (pre- vs. post-1992 national vaccine rollout). Time-to-waning analyses were performed using Kaplan–Meier methods. Results: HBsAg and anti-HBc were positive in 4.1% and 31.7% of patients, respectively; 3.7% were HCV seropositive. No HBsAg seroconversions occurred, and 2.1% of initially anti-HBc-negative patients seroconverted. Among patients with isolated anti-HBc, 80.9% developed protective anti-HBs titers, and none became HBsAg- or HBV DNA-positive. Waning anti-HBs titers occurred in 67.5% (median: 7.3 months), with 87.4% demonstrating a serologic response following documented vaccine delivery. Patients born after 1992 showed higher isolated anti-HBs positivity and lower anti-HBc prevalence. Ethnic subgroup analysis showed higher exposure rates but similar booster response among minority patients. Conclusions: HBV serologic profiles in this hemodialysis cohort reflected the interplay of immunosuppression, vaccination practices, and evolving epidemiologic trends. Subgroups exhibited variable vaccine responses, differing patterns of antibody waning, and a low incidence of new infections. These findings support tailored, population-specific HBV monitoring and prevention strategies in dialysis care. Full article

Background: Despite its high vaccination coverage, pertussis remains a public health concern due to waning vaccine-induced immunity and the emergence of pertactin (Prn)-negative strains. Nevertheless, anti-Prn antibodies and memory B cells elicited by vaccinations may contribute to long-term immunity and protection against Prn-positive strains. While most vaccination studies focus on serum antibodies, data on memory B cells remain limited. Methods: In this study, we implemented a flow cytometry-based approach to characterize Prn-specific B-cell fluctuations following Tdap booster vaccination in five healthy adults. Total and Prn- and tetanus toxoid fragment C (TTC)-specific plasma cells and memory B cells were analyzed at baseline and at 7, 14, 21, and 90 days post-vaccination using Prn Klickmers^® and TTC tetramers. Following this, cellular responses were correlated with antigen-specific serum IgG and IgA levels. Results: Prn-specific and TTC-specific memory B cells increased on days 14 and 7 post-vaccination, respectively, accompanied by a phenotypic shift from IgMD+ to IgG+ cells. Clear expansions of total as well as Prn- and TTC-specific plasma cells occurred on day 7. These plasma cells primarily comprised IgG+, but an increase in Prn-specific IgA+ plasma cells was also observed. The numbers of Prn-specific IgG+ memory B cells on day 7 post-vaccination correlated weakly with serum anti-Prn IgG levels at later time points. Conclusion: To our knowledge, this is the first study to use flow cytometry to evaluate Prn-specific B-cell responses and report their fluctuations over time following vaccination. These findings support the potential of this method to complement serological assays and improve our understanding of vaccine-induced immunity. Full article

Pertussis, caused by Bordetella pertussis, remains a public health concern despite long-standing vaccination programs. After a marked decline during the COVID-19 pandemic, a resurgence was observed in Europe and Italy, with a sharp increase in 2024. This study describes pertussis epidemiological trends in the Tuscany Region (Italy) from 2019 to 2024 to identify high-risk groups and inform prevention strategies. A retrospective population-based analysis was conducted using cases reported to the national surveillance system (PREMAL). Incidence rates were calculated using ISTAT population data, and demographic, temporal, and clinical characteristics were analyzed. Overall, 669 cases were reported (mean annual incidence rate: 3.03/100,000 (IC 95% 2.47–3.59; period incidence rate: 18.2/100,000 (IC 95% 16.81–19.56)), with 89% occurring in 2024 (16.34/100,000 (IC 95% 15.03–17.65)). No sex differences were observed, and most cases were reported in Central Tuscany (64%). Children under 15 years accounted for 87% of cases. The highest incidence was observed among 10–14-year-olds, while infants < 1 year, particularly those under 4 months, showed the highest burden in narrower age strata. Hospitalizations occurred in 12.6% of cases, decreasing substantially in 2024. The 2024 resurgence likely reflects waning immunity, disruptions to routine vaccinations during the pandemic, and reduced pathogen circulation in previous years due to containment and isolation measures related to the pandemic. Strengthening surveillance and improving booster and maternal vaccination coverage are essential to protect vulnerable populations. Full article

Background: Measles remains a global public health threat despite the availability of an effective vaccine and substantial progress toward elimination in many countries. Outbreaks in highly vaccinated settings suggest that waning vaccine-induced immunity, particularly among adults, may create silent susceptibility gaps capable of sustaining viral transmission. Aim: To evaluate age- and cohort-specific patterns of measles-specific antibody levels in Mexican adults and to examine evidence suggesting lower vaccine-induced antibody levels in younger vaccinated cohorts. Methods: A cross-sectional seroepidemiological study was conducted among 302 voluntary blood donors aged 18–70 years. Demographic, clinical, and vaccination data were collected through structured interviews. Serum anti-measles-virus (MV) IgG levels were quantified using a commercial ELISA. Antibody concentrations were analyzed according to age, sex, vaccination history, self-reported measles infection, and historical vaccination strategies. Multivariate linear models were applied to identify factors associated with IgG levels. Results: Anti-MV IgG seropositivity (>200 mIU/mL) was 67.2%, with a geometric mean concentration (GMC) of 270.43 mIU/mL. A positive correlation was observed between age and antibody levels (r_s = 0.161, p = 0.005). Individuals born before the introduction of the measles vaccine (pre-1970) had significantly higher GMCs (1096.63 mIU/mL) than younger cohorts. A history of natural infection tended to be associated with higher antibody levels (GMC: 428.38 vs. 257.24 mIU/mL; p = 0.051). In multivariate analysis, historical vaccination strategy emerged as the primary factor associated with antibody levels, whereas age alone was not significant. Conclusions: Cohort-specific differences in measles IgG levels suggest generational patterns of immunity and are consistent with diminished vaccine-induced antibody levels in younger adults in the absence of natural boosting. These findings highlight the importance of ongoing serological surveillance in post-elimination settings and underscore the need for targeted public health interventions. Full article

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in infants and young children worldwide and continues to impose a substantial disease burden despite recent advances in preventive strategies. Natural infection does not confer durable protective immunity, resulting in repeated reinfections, with the most severe disease occurring during early infancy. This review examines antibody-mediated prevention of RSV infection, with particular emphasis on vaccine development and maternal immunization. We reviewed current evidence on RSV pathogenesis, immune evasion, and antigenic characteristics relevant to vaccine design, focusing on viral surface glycoproteins targeted by preventive strategies. Recent data on licensed vaccines, long-acting monoclonal antibodies, and maternal immunization approaches were also evaluated. The RSV fusion (F) glycoprotein is the principal target of neutralizing antibodies and underpins currently licensed vaccines and monoclonal antibody products. Although circulating RSV strains show gradual antigenic evolution, primarily in the attachment protein, the F protein remains relatively conserved, resulting in only modest reductions in neutralization by human polyclonal sera over time. Constrained evolution of the F protein likely contributes to the sustained effectiveness of F-based interventions. However, waning F-specific neutralizing antibody titers contribute to susceptibility to reinfection, underscoring the importance of passive immunization strategies during early life. Maternal vaccination and long-acting monoclonal antibodies represent key advances in protecting young infants against RSV, but challenges remain in achieving equitable global implementation. Continued evaluation of antigenic evolution, the durability of protection, and optimization of maternal and infant immunization strategies will be critical for long-term disease control. Full article

Inconsistent presentation of STAT3 variants in clinical settings makes them challenging to use in diagnostics and the prevention of unfavorable outcomes. Patients harboring the STAT3^R152W variant display a range of autoimmune disorders, including type 1 diabetes, hemolytic anemia, and thrombocytopenia. Because of a complex interplay of genetic and environmental cofactors, it is difficult to discern the direct role STAT3 plays in the development of those conditions. Here, we report a mouse model of the STAT3^R152W variant and describe its hematopoietic populations throughout adulthood. We observed profound changes in both innate and adaptive immunity, including increased splenic Th17 component consistent with a gain-of-function mutation, as described in the literature. At the same time, the mice did not develop obvious symptoms of autoimmunity. R152W mutants show lowered hemoglobin and hematocrit, indicating susceptibility to anemia, but also an increased number of thrombocytes, contradictory to reports of autoimmune thrombocytopenia. We showcase how those changes develop and wane in time, and the differences between male and female animals. Our findings paint the STAT3^R152W variant as a cause of severe immune dysregulation, but only as a cofactor in the development of autoimmunity. Full article

Introduction: Cholera remains a major public health threat in endemic settings, and oral cholera vaccine (Shanchol™) campaigns are increasingly used amid constrained global supply. However, practical decisions on revaccination require clearer, setting-specific estimates of how rapidly vaccine-induced vibriocidal antibodies peak and wane. Methods: We conducted a prospective cohort kinetics analysis in Lukanga Swamps (Central Province, Zambia), enrolling adults (18–65 years) stratified by prior Shanchol™ exposure (0, 1, or 2 previous doses). All participants received two Shanchol™ doses 14 days apart, with serum collected at baseline and days 14, 28, 60, and 90 (end of follow-up). Ogawa and Inaba vibriocidal titres were measured using a complement-based assay and analysed on the log10 scale. Serotype-specific mixed-effects models with natural cubic splines for time (knots: 14, 28, 60 days) assessed trajectories by prior-dose strata, adjusting for age, sex, and HIV status. Peak timing and post-peak half-life were derived from model-based predictions with participant-level bootstrap CIs (1000 replications). Results: The analysis included 225 participants: 68 (30.2%) with zero prior doses, 89 (39.6%) with one, and 68 (30.2%) with two; median age was 33 years (IQR 25–49), 56.4% were female, and 19.2% were HIV-positive. Modelled titres for both serotypes rose steeply after vaccination, peaking around day 36–37 across prior-dose strata. Ogawa titres reached half of peak by about day 73–78, corresponding to post-peak half-lives of 37–41 days; Inaba declined more slowly with half-lives of 42–46 days. Confidence intervals overlapped across prior-dose strata, indicating minimal differences by vaccination history. Conclusions: In this cholera-endemic adult population, Shanchol™ induced vibriocidal responses that peaked at ~5 weeks and waned over the following 5–7 weeks, with broadly similar kinetics regardless of prior vaccination and slightly slower decay for Inaba than Ogawa. These parameters can inform booster timing in hotspot settings. Full article

Background: Despite the availability of a killed whole-virus (KV) vaccine, diarrhea caused by equine rotavirus group A (ERVA) remains a significant health concern for foals in the United States. The vaccine is administered to pregnant mares, with foals protected by passive transfer of colostral antibodies. However, KV-induced immunity is only partially protective and maternal antibody levels in foals are often low and wane rapidly. To address these limitations, we developed a mRNA-based ERVA vaccine encoding the highly conserved VP8* protein to evaluate whether it can provide improved immune protection. Methods: Pregnant mares (n = 12 per group) were immunized either at months 8 and 10 of gestation with the VP8* mRNA or at months 8, 9, and 10 of gestation with the KV. Serum samples were collected from mares before and after immunization and from their foals at ages 1, 35, and 49 days. Serum samples were tested by indirect ELISA for VP8*-specific relative antibody concentrations and relative concentrations were compared for effects of study group and sample-time using linear mixed-effects regression. To detect functional antibodies against ERVA, a virus neutralization titer assay was performed to compare titers between mares vaccinated with the mRNA vaccine (and their foals) and unvaccinated control mares (and their foals). Results: Mares vaccinated with VP8* mRNA had significantly (p < 0.05) higher antibody concentrations after foaling than mares in the KV group, and foals of VP8* mRNA-vaccinated mares had significantly (p < 0.05) higher concentrations through age 49 days than foals in the KV group. In addition, the VP8* mRNA vaccine elicited higher titers of ERVA-neutralizing antibodies against both G3 and G14 strains. Conclusions: Longer-lasting, higher concentrations of virus-neutralizing antibodies might provide superior duration of immunity to ERVA in foals from mares vaccinated with VP8* mRNA. Full article

Background: Whooping cough caused by Bordetella pertussis is re-emerging despite high vaccination coverage, with rising incidence in adolescents and adults in the acellular vaccine (aP) era. This narrative review synthesizes evidence on the drivers of this paradox and their implications for pertussis control. Methods: We conducted a structured (but not fully systematic) literature search and narrative synthesis of PubMed, Web of Science, and Embase for publications from January 2000 to February 2025 using terms related to “Bordetella pertussis,” “pertussis resurgence,” “acellular vaccine,” “waning immunity,” “ptxP3,” “pertactin-deficient,” “macrolide resistance,” and “whole-genome sequencing.” English-language, peer-reviewed studies, surveillance reports, genomic analyses, and immunological investigations were included. About 1900 records met broad eligibility criteria and were screened, and key studies were selected for narrative synthesis. Results: The resurgence appears to result from three convergent factors: (1) waning and non-sterilizing aP-induced immunity, which allows bacterial colonization and transmission; (2) vaccine-driven genomic evolution of B. pertussis, marked by global dominance of the ptxP3 lineage and widespread pertactin-deficient (PRN−) strains; and (3) emergence of macrolide-resistant clones, exemplified by the MT28-Shanghai strain. Whole-genome sequencing (WGS) has been central for defining these processes and clonal sweeps under combined vaccine and antibiotic pressure, supporting a three-driver framework of waning aP immunity, vaccine-driven evolution, and macrolide resistance. Conclusions: Pertussis resurgence illustrates pathogen adaptation to human interventions. Effective mitigation requires WGS-integrated global surveillance, re-evaluation of vaccine formulations to keep pace with antigenic change, and strengthened antibiotic stewardship, alongside development of next-generation vaccines that induce durable mucosal immunity and block transmission. Full article

RNA-based vaccination has been broadly applied in the COVID-19 pandemic. A characteristic of the immunization was fast-waning immunity. However, the time scale of this process varied considerably for virus subtypes and among individuals. Understanding the origin of this variability is crucial in order to improve future vaccination strategies. Here, we introduce a mathematical model of RNA-based vaccination and the kinetics of the induced immune response. In the model, antigens produced following vaccination give rise to an immune response leading to germinal center reactions and accordingly B-cell differentiation into memory B-cells and plasma cells. In a negative feedback loop, the antibodies synthesized by newly specified plasma cells shut down the germinal center reaction as well as antigen-induced differentiation of memory B-cell into plasma cells. This limits the build-up of long-lasting immunity and thus is accompanied by fast-waning immunity. The detailed data available on infection with and vaccination against SARS-CoV-2 enabled computational simulation of essential processes of the immune response. Through simulation, we analyzed to what extent a single- or double-dose vaccination provides protection against infection. We find that variability in the immune response in individuals, originating, e.g., in different immune-cell densities, results in a broad log-normal-like distribution of the vaccine-induced protection times that peaks around 100 days. Protection times decrease for virus variants with mutated antibody-binding sites or increased replication rates. Independent of these virus specifics, our simulations suggest optimal timing of a second dose about 5 weeks after the first in agreement with clinical trials. Full article