Human Vaccines & Immunotherapeutics最新文献

Estimates of the added benefit from COVID-19 vaccine booster doses can inform seasonal vaccine recommendations. We set out to estimate COVID-19 vaccine effectiveness (VE), avoiding common sources of bias. We chose a modified screening method, using only vaccinated cases of symptomatic COVID-19 recorded in the mandatory infectious disease reporting system, with data from a vaccination registry. Effect estimates were obtained by Bayesian logistic regression, comparing outcomes within dose strata between immunized (15-21d after vaccination) and not yet immunized (up to 7d). VE estimates were calculated recursively and relative VE estimates were obtained to quantify the added benefit of booster doses. We found VE for clinical illness to be around 90% during the predominance of the SARS-CoV-2 Alpha variant. During the Delta period, VE was distinctly lower, but did not decrease much further. The first booster dose added substantial protection during the Delta period, but that benefit became marginal during the Omicron period in the 18+. The effect of second booster doses, which became widespread only during the Omicron period, was modest. Using a novel, vaccinated-only study design we found that two doses of a COVID-19 vaccine offered substantial protection from symptomatic COVID-19, even during the Omicron period. One booster dose was highly effective during the Delta period, but the effect became modest during the Omicron period, when second booster doses offered, but a marginal benefit.

Vaccination remains one of the most cost-effective methods for disease prevention. However, utilization of self-paid vaccines, including EV71, varicella, influenza, and DTaP-IPV-Hib in this study, remains insufficient among children under six in China. To investigate the determinants of willingness to vaccinate (WTV) for self-paid vaccines and assess cost-WTV heterogeneity, we conducted structured-questionnaire surveys with 2212 randomly selected households in Hangzhou, each with at least one child under six. Multiple regression analysis was used to identify the key determinants of WTV, and a mixed-effect model was employed to analyze the correlation between vaccine cost and WTV, further segmenting the data with unsupervised clustering techniques. Our findings highlighted impact of vaccination cost as a pivotal factor influencing the WTV for self-paid vaccines. We categorized the population into four groups based on their sensitivity to vaccine cost. Families with one child, children aged 1-3 y, highly-educated parents, and higher socioeconomic status consistently exhibited high WTV. Our analysis offers targeted strategies to enhance vaccine uptake and improve immunization coverage.

People with underlying diseases are at-increased-risk of suffering from herpes zoster (HZ). However, the economic impact of HZ on these populations is not well described. This study aimed to quantify the clinical and economic impact of HZ in patients with comorbidities (diabetes, chronic obstructive pulmonary disease, heart disease, kidney disease, asthma) and immune disorders (inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, psoriasis, COVID-19 and psoriatic arthritis) in Spain. This is an observational, retrospective case-control study using the BIG-PAC electronic records from 01 Jan 2014 to 31 Aug 2021. Healthcare resource use and costs over 12 months following HZ diagnosis were compared between patients and controls, matched by propensity scores. The total annual economic burden was estimated using HZ-related costs per patient and HZ crude incidence over the study period, together with the estimated prevalence of each comorbidity in the Spanish population aged ≥18 y. Mean incremental costs per HZ episode were €1,108 in patients with comorbidities and €1,203 in patients with immune disorders. Indirect costs accounted for 4.7% and 22.9% of incremental costs in people with comorbidities and immune disorders, respectively. Mean annual crude HZ incidence rates were 613.6 cases per 100,000 people with comorbidities and 659.0 cases per 100,000 people with autoimmune disorders. Total annual costs due to HZ in these populations were estimated at €121 million. HZ may cause a significant economic burden in Spain from a societal perspective in patients with underlying conditions, highlighting the importance of improving vaccination programs.

There has been a considerable controversy about vaccination practices of children with special health-care needs (CSHCNs) in China. We aim to describe current vaccination recommendations, immunization status, and vaccination safety of CSHCNs in Wuxi. We conducted a cross-sectional study of CSHCNs aged <18 y visiting the vaccination consultation clinic (VCC) at Wuxi Children's Hospital in 2020-2023. Demographic information was collected from Electronic Medical Records, vaccination data was obtained from Vaccination Integrated Service Management Information System of Jiangsu Province, China. Safety monitoring data was acquired from China National Adverse Events Following Immunization Information System (CNAEFIS). Descriptive data were presented as percentages, and Poisson test was used to compare the cumulative incidence of AEFIs between groups. Four thousand one hundred and twenty-two participants were included and the majority (73.0%) were under 12 months. The top three diseases consulted were those relating to the certain conditions originating in the perinatal period, developmental anomalies, and diseases of the blood or blood-forming organs. Only 6.1% had previously received all age-eligible vaccine doses before seeking evaluation. According to the vaccination guidance issued by the VCC, 59.9% were recommended to continue vaccine normally, partial vaccination was recommended for 37.2%, and 4.1% were advised to delay. A total of 3927 CSHCNs received 62,744 vaccine doses after consultation. None had serious adverse events and the cumulative incidence of AEFIs was higher than the general population of children. Specialist consultation is helpful to improve the vaccine uptake. Further research on strategies to improve the vaccination coverage of CSHCNs is warranted.

Cholangiocarcinoma (CCA) has a complex tumor microenvironment that critically influences tumor progression and therapeutic resistance. Glycosylation abnormalities have been linked to cancer growth and progression. This work was designed to develop a prognostic model based on glycosylation-related genes (GRGs) for predicting CCA outcomes and immunotherapy responses. Glycosylation patterns in macrophage subsets of CCA were analyzed via scRNA-seq. Key genes were identified by integrating module genes from WGCNA and DEGs. A risk model for CCA was established utilizing LASSO Cox regression. In vitro tests were conducted to validate the function of PGK1. The immune checkpoint blockade group exhibited elevated M1 signature scores and higher glycosylation levels. A risk model incorporating five genes (ANXA3, PGK1, PLAUR, CREB5, SPP1) for CCA was established. The high macrophage glycosylation-related risk score group had a considerable infiltration of M0 macrophages. In vitro experiments confirmed that PGK1 advanced glycation end products accumulation, drove M2 polarization of macrophages, and increased CCA cell proliferation and migration. This work proposes a glycosylation-based risk model for predicting CCA prognosis and directing therapeutic strategies. PGK1 is highlighted as a potential therapeutic target in CCA.

Antigen anisotropy, the directional dependence of protein conformation, epitope exposure, and conformational dynamics, is an under-appreciated determinant of vaccine immunogenicity. Preserving this geometric fidelity may influence outcomes such as neutralization breadth, affinity maturation, and B/T-cell response quality. Native antigens engage B-cell receptors, T-cell receptors, and MHC through oriented interactions that rely on spatial and dynamic constraints for effective immune recognition. This framework is increasingly relevant amid widespread use of nucleoside-modified mRNA vaccines, as recent studies suggest platform-specific deviations in antigen geometry and processing. Platform interventions including chemical inactivation (e.g., formaldehyde and β-propiolactone), formulation and storage conditions, and mRNA design choices (e.g., N¹-methylpseudouridine incorporation, codon optimization) can introduce perturbations that influence folding, glycan shielding, epitope presentation, and hydrodynamic behavior. These effects can generate antigen ensembles that diverge from native forms, and may plausibly contribute to differences in response breadth and quality. Prioritizing anisotropy preservation offers a complementary design principle for next generation vaccines, one that seeks to more closely recapitulate the geometric and dynamic features of natural infection and may improve the predictability and durability of protective immunity.

This study examined whether COVID-19 Vaccine Hesitancy (VH) and COVID-19-related factors interact to influence COVID-19 booster doses uptake among university students in Canada, from a syndemic perspective. A cross-sectional survey was conducted among 4453 students at the University of Waterloo in 2024. VH was measured toward both COVID-19 primary and booster doses. Change in VH scores were computed to capture shifts in hesitancy over time. Logistic regression models assessed the main effects of VH and COVID-19-related factors on booster uptake. Interactions were tested using additive and multiplicative scales. Increased VH was associated with a 23% decrease in booster uptake. Younger ages, not being hospitalized due to COVID-19, not receiving the influenza vaccine, noncompliance with COVID-19 guidelines, and belief in conspiracy theories predicted lower booster uptake. Significant interactions were found between change in VH scores and COVID-19 diagnosis and hospitalization history, guideline adherence, and conspiracy beliefs. For students who did not receive booster doses, the change in VH was greater among those who reported following public health guidance than those who did not. Similarly, for students who did not receive booster doses, the change in VH was greater among those who reported not believing in conspiracy theories compared to those who did. The findings support a syndemic model, indicating that VH and COVID-19-related experiences jointly influence booster uptake. Targeted interventions such as rebuilding trust, addressing misinformation, and reducing stigma may improve booster uptake even if not all barriers are addressed. Further research is needed to examine these interactions.

Following the January 2025 approval of the first male HPV vaccine in the Chinese mainland, we investigated vaccination willingness and its influencing factors among community-dwelling men. We conducted a cross-sectional study in Beijing, recruiting 480 community-based male residents and 399 men who have sex with men (MSM). Participants completed a questionnaire assessing HPV knowledge and the Health Belief Model (HBM) constructs. Multivariable logistic regression was performed to identify determinants of willingness. We found a high level of vaccination willingness, which was notably higher among MSM (90.73%) than the community-recruited male population (87.29%). Critically, willingness surpassed awareness, indicating significant latent demand despite low overall HPV knowledge. HBM analysis showed that perceived benefits promoted willingness in both groups, while self-efficacy of prevention paradoxically acted as an inhibitor. MSM reported higher perceived susceptibility and benefits, but lower severity, compared to community-recruited men. Determinants diverged significantly: income and sexual behavior were unique drivers for community-recruited men, whereas HPV knowledge and STI self-testing drove willingness in MSM. This study confirms high post-approval vaccination willingness but highlights distinct influencing factors. Findings suggest the need for differentiated strategies: universal approaches should highlight vaccine benefits to convert latent demand, while targeted education for MSM must focus on improving knowledge accuracy.

Globally, childhood immunization remains a major public health concern, with 19.4 million children not fully vaccinated in 2018, the majority from low- and middle-income countries. Ethiopia, in particular, reports alarmingly low immunization coverage, with nearly one million children unvaccinated and vaccine-preventable diseases accounting for approximately 16% of childhood mortality. This study aimed to examine the spatiotemporal distribution and associated factors of immunization among children aged 12-23 months in Ethiopia. Data were obtained from four rounds of the Ethiopia Demographic and Health Survey (EDHS) conducted between 2000 and 2016, comprising a sample of 6767 children. Spatial analysis was performed using ArcGIS, and statistical analysis was carried out using SAS software. The spatial partial proportional odds model was used due to the violation of the proportional odds assumption. Full immunization coverage showed a gradual increase from 14.6% in 2000 to 39.4% in 2016. Spatial clustering of immunization coverage was observed in all survey years, indicating nonrandom distribution across regions. Children born to mothers with primary education were significantly more likely to be fully vaccinated than those whose mothers had no education. The model identified several significant predictors of immunization status, including region, residence, maternal education, religion, household wealth, maternal employment, place of delivery, antenatal care, and health worker visits. A significant negative spatial auto-covariance suggested that areas with low coverage were often surrounded by higher-coverage zones. Targeted interventions, particularly in identified hotspot areas, and increased public health education are recommended, along with further research using recent data.

Heterologous boosting with aerosolized or intramuscular Ad5-nCoV following a two-dose CoronaVac prime has been shown to induce higher antibody levels than a homologous CoronaVac booster. However, no specific modeling has been reported to characterize the kinetics of antibody waning for these heterologous regimens. By integrating longitudinal serological data from three randomized trials conducted in Jiangsu, China (NCT04892459, NCT04952727, NCT05043259), we applied linear mixed-effects models to establish both exponential and power-law decay models for neutralizing antibodies, including live-virus neutralizing antibodies against the prototype, Delta, and Omicron BA.1 variants, and pseudovirus neutralizing antibodies against Omicron BA.4/5 variant, respectively. The findings showed that the power-law model exhibited a superior fit over the exponential model across all antibody types (all ΔAICc < 0). According to the power-law model (at day 90), the half-lives of live-virus neutralizing antibodies against the wild-type SRAS-CoV-2 strain was 195 d (95% CI: 185-210) in the aerosolized Ad5-nCoV group, 226 d (220-252) in the intramuscular Ad5-nCoV group, versus 230 d (95% CI: 222-257) in the three-dose CoronaVac group. For the Omicron BA.1 variant, the half-life was 314 d (248-453) in the aerosolized Ad5-nCoV group, 168 d (159-180) in the intramuscular Ad5-nCoV group, compared to 196 d (174-230) in the three-dose CoronaVac group. Our model indicated that the heterologous booster with Ad5-nCoV after two-dose CoronaVac, particularly the aerosolized Ad5-nCoV, induces longer-lasting neutralizing antibodies than three-dose CoronaVac, preferably characterized by power-law decay models.