Modeling antigen-specific T cell dynamics following Hepatitis B Vaccination indicates differences between conventional and regulatory T cell dynamics.

Our study aims to investigate the dynamics of conventional memory T cells (Tconv) and regulatory memory T cells (Treg) following activation, and to explore potential differences between these two cell types. To achieve this, we developed advanced statistical mixed models based on mathematical models of ordinary differential equations (ODE), which allowed us to transform post-vaccination immunological processes into mathematical formulas. These models were applied to in-house data from a de novo Hepatitis B vaccination trial. By accounting for inter- and intra-individual variability, our models provided good fits for both antigen-specific Tconv and Treg cells, overcoming the challenge of studying these complex processes. Our modeling approach provided a deeper understanding of the immunological processes underlying T cell development after vaccination. Specifically, our analysis revealed several important findings regarding the dynamics of Tconv and Treg cells, as well as their relationship to seropositivity for Herpes Simplex Virus Type 1 (HSV-1) and Epstein-Barr Virus (EBV), and the dynamics of antibody response to vaccination. Firstly, our modeling indicated that Tconv dynamics suggest the existence of two T cell types, in contrast to Treg dynamics where only one T cell type is predicted. Secondly, we found that individuals who converted to a positive antibody response to the vaccine earlier had lower decay rates for both Tregs and Tconv cells, which may have important implications for the development of more effective vaccination strategies. Additionally, our modeling showed that HSV-1 seropositivity negatively influenced Tconv cell expansion after the second vaccination, while EBV seropositivity was associated with higher Treg expansion rates after vaccination. Overall, this study provides a critical foundation for understanding the dynamic processes underlying T cell development after vaccination.

Humoral immune response against SARS-CoV-2 after adapted COVID-19 vaccine schedules in healthy adults: The IMCOVAS randomized clinical trial.

BACKGROUND: To overcome supply issues of COVID-19 vaccines, this partially single blind, multi-centric, vaccine trial aimed to evaluate humoral immunogenicity using lower vaccine doses, intradermal vaccination, and heterologous vaccine schedules. Also, the immunity after a booster vaccination was assessed. METHODOLOGY: 566 COVID-19-naïve healthy adults were randomized to 1 of 8 treatment arms consisting of combinations of BNT162b2, mRNA-1273, and ChAdOx1-S. Anti-Receptor-Binding Domain immunoglobulin G (RBD IgG) titers, neutralizing antibody titres, and avidity of the anti-RBD IgGs was assessed up to 1 year after study start. RESULTS: Prolonging the interval between vaccinations from 28 to 84 days and the use of a heterologous BNT162b2 + mRNA-1273 vaccination schedule led to a non-inferior immune response, compared to the reference schedule. A low dose of mRNA-1273 was sufficient to induce non-inferior immunity. Non-inferiority could not be demonstrated for intradermal vaccination. For all adapted vaccination schedules, anti-RBD IgG titres measured after a first booster vaccination were non-inferior to their reference schedule. CONCLUSION: This study suggests that reference vaccine schedules can be adapted without jeopardizing the development of an adequate immune response. Immunity after a booster vaccination did not depend on the dose or brand of the booster vaccine, which is relevant for future booster campaigns. The trial is registered in the European Union Clinical Trials Register (number 2021-001993-52) and on clinicaltrials.gov (NCT06189040).

Multi-View Learning to Unravel the Different Levels Underlying Hepatitis B Vaccine Response.

The immune system acts as an intricate apparatus that is dedicated to mounting a defense and ensures host survival from microbial threats. To engage this faceted immune response and provide protection against infectious diseases, vaccinations are a critical tool to be developed. However, vaccine responses are governed by levels that, when interrogated, separately only explain a fraction of the immune reaction. To address this knowledge gap, we conducted a feasibility study to determine if multi-view modeling could aid in gaining actionable insights on response markers shared across populations, capture the immune system's diversity, and disentangle confounders. We thus sought to assess this multi-view modeling capacity on the responsiveness to the Hepatitis B virus (HBV) vaccination. Seroconversion to vaccine-induced antibodies against the HBV surface antigen (anti-HBs) in early converters (n = 21; <2 months) and late converters (n = 9; <6 months) and was defined based on the anti-HBs titers (>10IU/L). The multi-view data encompassed bulk RNA-seq, CD4+ T-cell parameters (including T-cell receptor data), flow cytometry data, and clinical metadata (including age and gender). The modeling included testing single-view and multi-view joint dimensionality reductions. Multi-view joint dimensionality reduction outperformed single-view methods in terms of the area under the curve and balanced accuracy, confirming the increase in predictive power to be gained. The interpretation of these findings showed that age, gender, inflammation-related gene sets, and pre-existing vaccine-specific T-cells could be associated with vaccination responsiveness. This multi-view dimensionality reduction approach complements clinical seroconversion and all single modalities. Importantly, this modeling could identify what features could predict HBV vaccine response. This methodology could be extended to other vaccination trials to identify the key features regulating responsiveness.

Integrated Drivers of Basal and Acute Immunity in Diverse Human Populations.

Prior studies have identified genetic, infectious, and biological associations with immune competence and disease severity; however, there have been few integrative analyses of these factors and study populations are often limited in demographic diversity. Utilizing samples from 1,705 individuals in 5 countries, we examined putative determinants of immunity, including: single nucleotide polymorphisms, ancestry informative markers, herpesvirus status, age, and sex. In healthy subjects, we found significant differences in cytokine levels, leukocyte phenotypes, and gene expression. Transcriptional responses also varied by cohort, and the most significant determinant was ancestry. In influenza infected subjects, we found two disease severity immunophenotypes, largely driven by age. Additionally, cytokine regression models show each determinant differentially contributes to acute immune variation, with unique and interactive, location-specific herpesvirus effects. These results provide novel insight into the scope of immune heterogeneity across diverse populations, the integrative effects of factors which drive it, and the consequences for illness outcomes.

Global Perspectives on Immunization During Pregnancy and Priorities for Future Research and Development: An International Consensus Statement.

Immunization during pregnancy has been recommended in an increasing number of countries. The aim of this strategy is to protect pregnant women and infants from severe infectious disease, morbidity and mortality and is currently limited to tetanus, inactivated influenza, and pertussis-containing vaccines. There have been recent advancements in the development of vaccines designed primarily for use in pregnant women (respiratory syncytial virus and group B Streptococcus vaccines). Although there is increasing evidence to support vaccination in pregnancy, important gaps in knowledge still exist and need to be addressed by future studies. This collaborative consensus paper provides a review of the current literature on immunization during pregnancy and highlights the gaps in knowledge and a consensus of priorities for future research initiatives, in order to optimize protection for both the mother and the infant.

Surveillance of effects of HPV vaccination in Belgium.

BACKGROUND: Early effects of HPV (human papillomavirus) vaccination are reflected by changes observable in young women attending cervical cancer screening. SUBJECT AND METHODS: The SEHIB study included HPV geno-typing of ∼6000 continuous and 650 pathological cervical cell specimen as well as biopsies, collected from women in Belgium in 2010-2014. Data were linked to vaccination status. RESULTS: HPV vaccination offered protection among women aged <30years against infection with HPV16 (vaccine effectiveness [VE]=67%, 95% CI: 48-79%), HPV18 (VE=93%, 95% CI: 52-99%), and high-risk HPV (VE=16%, 95% CI: 2-29%). Vaccination protected also against cytological lesions. Vaccination protected against histologically confirmed lesions: significantly lower absolute risks of CIN1+ (risk difference [RD]=-1.6%, 95% CI: -2.6% to -0.7%) and CIN3+ associated with HPV16/18 (RD=-0.3%, 95% CI -0.6% to -0.1%). Vaccine effectiveness decreased with age. Protection against HPV16 and 18 infection was significant in all age groups, however no protection was observed against cytological lesions associated with these types in age-group 25-29. CONCLUSION: The SEHIB study demonstrates the effectiveness of HPV vaccination in Belgian young women in particular in age group 18-19. Declining effectiveness with increasing age may be explained by higher tendency of women already exposed to infection to get the vaccine.

Insured versus uninsured patients in the emergency room: is there a difference?

OBJECTIVE: To define the differences in emergency room usage patterns between patients with and without medical insurance coverage. METHODS: A retrospective analysis of the database of 34 642 consecutive patient visits to an urban hospital emergency room over a period of 509 days. Arrival times and admission rates were compared for insured and uninsured patients. RESULTS: A total of 46.8% of insured patients arrived at night or during the weekend versus 51.7% of the uninsured. Slightly more insured patients were admitted (18.6 versus 15.4%), both after their visit during the daytime (20.6 versus 17.1%) and outside daytime hours (16.3 versus 13.8%). The uninsured population was younger. CONCLUSION: Uninsured patients arrived more frequently during weekends and at night than insured patients. They were on average less likely to be admitted to the hospital. Demographic differences between both groups seemed to play an important role in the admission rate. Despite differences in emergency room usage patterns, it cannot be concluded that either group used the emergency room in excess of the other.

Long-term efficacy of hepatitis B vaccine, booster policy, and impact of hepatitis B virus mutants.

The long-term efficacy of hepatitis B vaccine, long-term effectiveness of hepatitis B immunisation programmes, immune memory induced by hepatitis B vaccine, current booster policies, and impact of hepatitis B virus mutants on immunisation programmes were reviewed at the Viral Hepatitis Prevention Board (VHPB) meeting in Sevilla, Spain, March 2004. The main focus was on universal vaccination programmes with data being presented from Italy, Saudi Arabia, Singapore, Spain, Taiwan, Thailand, The Gambia, and USA (Alaska).

The seroepidemiology of primary varicella-zoster virus infection in Flanders (Belgium).

UNLABELLED: The age-specific seroprevalence of varicella-zoster virus (VZV) antibodies was assessed in a sample of the Flemish (Belgian) population. ELISA tests were used to analyse 1673 sera from subjects aged 1 to 44 years (October 1999-April 2000). Chickenpox infections in Flanders appear to affect children at a younger age than in other European countries since 47.37% (95% CI: 37.33-57.41) is already immune at 2 years of age. For older age-groups, the prevalence is similar to that of most European countries: 80.19% (95% CI: 72.60-87.78) at 5 years, 92.52% (95% CI: 87.54-97.51) at 9 years and 100%> or =40 years. The accuracy of non-positive recollections of varicella histories among Flemish 10 to 17-year olds was examined on the basis of a second (residual) serum bank. In this group, VZV seroprevalence was almost always 100% (or nearly 100%), irrespective of age, degree of reliability (negative or uncertain answers) or level of ascertainment (child personally or parents). The limited size of this second data set did not allow for an accurate assessment of the negative predictive value of such recollections. CONCLUSION: since varicella-zoster virus predominantly affects very small children and is generally perceived as benign, the required high coverage rate of a universal childhood varicella vaccination programme may be hard to attain. Adolescent strategies can minimise the population risks involved but the accuracy of non positive antecedents of chickenpox needs to be documented to assess the efficiency of such strategies.