AUTHOR=van der Heiden Marieke , de Rond Lia G. H. , van Zelm Menno C. , Berbers Guy A. M. , Boots Annemieke M. H. , Buisman Anne-Marie 

TITLE=Age-Dependent Pre-Vaccination Immunity Affects the Immunogenicity of Varicella Zoster Vaccination in Middle-aged Adults

JOURNAL=Frontiers in Immunology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00046

DOI=10.3389/fimmu.2018.00046

ISSN=1664-3224

ABSTRACT=Background
Prevention of infectious diseases is of high priority in the rapidly ageing 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 IFNγ-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 IFNγ producing cell numbers was observed post-vaccination in the middle-aged adults. Remarkably, long-term enhancement of VZV-specific IFNγ producing cell numbers was induced only in participants with low numbers of VZV-specific pre-vaccination IFNγ 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 IFNγ producing cells. Finally, a high CD4/CD8 T-cell ratio was associated with low numbers of pre-vaccination VZV-specific IFNy 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 IFNγ 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.