Dataset Information

An Explorative Biomarker Study for Vaccine Responsiveness after a Primary Meningococcal Vaccination in Middle-Aged Adults.

ABSTRACT:

Introduction

Prevention of infectious diseases in the elderly is essential to establish healthy aging. Yet, immunological aging impairs successful vaccination of the elderly. Predictive biomarkers for vaccine responsiveness in middle-aged adults may help to identify responders and non-responders before reaching old age. Therefore, we aimed to determine biomarkers associated with low and high responsiveness toward a primary vaccination in middle-aged adults, for which a tetravalent meningococcal vaccine was used as a model.

Methods

Middle-aged adults (50-65?years of age, N?=?100), receiving a tetravalent meningococcal vaccination, were divided into low and high responders using the functional antibody titers at 28?days postvaccination. A total of 48 parameters, including absolute numbers of immune cells and serum levels of cytokines and biochemical markers, were determined prevaccination in all participants. Heat maps and multivariate redundancy analysis (RDA) were used to reveal immune phenotype characteristics and associations of the low and high responders.

Results

Several significant differences in prevaccination immune markers were observed between the low and high vaccine responders. Moreover, RDA analysis revealed a significant association between the prevaccination immune phenotype and vaccine responsiveness. In particular, our analysis pointed at high numbers of CD4 T cells, especially naïve CD4 and regulatory T subsets, to be associated with low vaccine responsiveness. In addition, low responders showed lower prevaccination IL-1Ra levels than high responders.

Conclusion

This explorative biomarker study shows associations between the prevaccination immune phenotype and vaccine responsiveness after a primary meningococcal vaccination in middle-aged adults. Consequently, these results provide a basis for predictive biomarker discovery for vaccine responsiveness that will require validation in larger cohort studies.

SUBMITTER: van der Heiden M

PROVIDER: S-EPMC5768620 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

An Explorative Biomarker Study for Vaccine Responsiveness after a Primary Meningococcal Vaccination in Middle-Aged Adults.

van der Heiden Marieke M Berbers Guy A M GAM Fuentes Susana S van Zelm Menno C MC Boots Annemieke M H AMH Buisman Anne-Marie AM

Frontiers in immunology 20180111

<h4>Introduction</h4>Prevention of infectious diseases in the elderly is essential to establish healthy aging. Yet, immunological aging impairs successful vaccination of the elderly. Predictive biomarkers for vaccine responsiveness in middle-aged adults may help to identify responders and non-responders before reaching old age. Therefore, we aimed to determine biomarkers associated with low and high responsiveness toward a primary vaccination in middle-aged adults, for which a tetravalent mening ...[more]

PMID: 29375578

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Project description:Vaccine responses are often reduced in the elderly, leaving part of the elderly population vulnerable to infectious diseases. Timely vaccination may offer a solution for strengthening memory immunity before reaching old age, which classifies middle-aged persons as a target age group for vaccine interventions. However, knowledge regarding the immunogenicity of primary immunizations in middle-aged adults is lacking. We determined the immunogenicity of a primary meningococcal vaccine towards which no or (very) low pre-vaccination immunity exists in middle-aged adults (NTR4636).A vaccine containing multiple meningococcal groups (tetravalent) conjugated to tetanus toxoid (MenACWY-TT) was administered to middle-aged adults (50-65?years of age, N?=?204) in a phase IV single-center and open-label study. Blood samples were taken pre-, 7?days, 28?days, and 1?year post-vaccination. Functional antibody titers were measured with the serum bactericidal assay (SBA). Meningococcal- and tetanus-specific antibody responses were determined with a fluorescent bead-based multiplex immunoassay. A bi-exponential decay model was used to estimate long-term protection.In the majority of the participants, the meningococcal vaccine clearly induced naïve responses to meningococci W (MenW) and meningococci Y (MenY) as compared to a booster response to meningococci C (MenC). After 28?days, 94, 99, and 97% of the participants possessed a protective SBA titer for MenC, MenW, and MenY, respectively, which was maintained in 76, 94, and 86% 1?year post-vaccination. At this 1-year time point, significantly lower SBA titers were found in participants without a pre-vaccination SBA titer. Overall, protective antibody titers were predicted to persist after 10?years in 40-60% of the participants. The SBA titers correlated well with the meningococcal-specific IgM responses, especially for MenW and MenY. Interestingly, these IgM responses were negatively correlated with age.Primary immunization with a tetravalent meningococcal vaccine was highly immunogenic in middle-aged adults, inducing protective antibody titers in the vast majority of the participants lasting for at least 1?year. The age-related decrease in highly functional IgM responses argues in favor of vaccination against de novo antigens before reaching old age and, hence, middle-aged persons are an age group of interest for future vaccine interventions to protect the aging population.

Project description:Background:Prevention of infectious diseases is of high priority in the rapidly aging population. Unfortunately, vaccine responses in the elderly are frequently diminished. Timely vaccination of middle-aged adults might improve the immune responses to vaccines, although knowledge on pathogen-specific immune responses and factors affecting these responses, in middle-aged adults is currently limited. We thus investigated the immune responses after vaccination with Zostavax consisting of live-attenuated varicella zoster virus (VZV). Methods:Blood samples were taken pre-, 14?days, 28?days, and 1?year after a primary VZV vaccination (Zostavax) at middle age (N?=?53, 50-65?years of age). VZV-specific IFN?-producing cells were measured by ELISpot, activated T-cells by flow cytometry, antibody levels and cytokine responses by fluorescent bead-based multiplex immunoassays, and whole blood cellular kinetics by TruCOUNT analysis. Results:Robust short-term enhancement of the VZV-specific IFN?-producing cell numbers was observed post-vaccination in the middle-aged adults. Remarkably, long-term enhancement of VZV-specific IFN?-producing cell numbers was induced only in participants with low numbers of VZV-specific pre-vaccination IFN?-producing cells, who were significantly older. These participants also showed enhancement of VZV-specific activated CD4 T-cells, contrary to "exhausted" VZV-specific CD8 T-cells in participants with high numbers of VZV-specific pre-vaccination IFN?-producing cells. Finally, a high CD4/CD8 T-cell ratio was associated with low numbers of pre-vaccination VZV-specific IFN?-producing cells. Conclusion:These results suggest that adults in their early sixties, who showed a high CD4/CD8 T-cell ratio and low numbers of VZV-specific IFN?-producing cells, benefit from VZV vaccination. This provides important knowledge on factors affecting VZV-specific immune responses in middle-aged adults as well as for strategies to strengthen immunity before reaching old age.

Dataset Information

An Explorative Biomarker Study for Vaccine Responsiveness after a Primary Meningococcal Vaccination in Middle-Aged Adults.

Introduction

Methods

Results

Conclusion

Publications

An Explorative Biomarker Study for Vaccine Responsiveness after a Primary Meningococcal Vaccination in Middle-Aged Adults.

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