Abstract
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). 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. 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 IFNγ-producing cells. 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.
Highlights
Prevention of infectious diseases in the elderly is of high priority to establish healthy aging in the rapidly aging population
A high CD4/CD8 T-cell ratio was associated with low numbers of pre-vaccination varicella zoster virus (VZV)-specific IFNγ-producing cells
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
Summary
Prevention of infectious diseases in the elderly is of high priority to establish healthy aging in the rapidly aging population. Knowledge on pathogen-specific immune responses in middle-aged adults and factors affecting these immune responses is limited. Understanding the VZV-specific immune responses and factors affecting this immunity is crucial to decrease the herpes zoster disease burden. Prevention of infectious diseases is of high priority in the rapidly aging population. Vaccination of middle-aged adults might improve the immune responses to vaccines, knowledge on pathogen-specific immune responses and factors affecting these responses, in middle-aged adults is currently limited. We investigated the immune responses after vaccination with Zostavax consisting of live-attenuated varicella zoster virus (VZV)
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