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

• Published in: Frontiers in immunology 2018-01, Vol.9, p.46-46
• Main Authors: van der Heiden, Marieke, de Rond, Lia G H, van Zelm, Menno C, Berbers, Guy A M, Boots, Annemieke M H, Buisman, Anne-Marie
• Format: Article
• Language: English
• Subjects: Aged; Aging - immunology; Antibodies, Viral - blood; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; cytokines; Herpes Zoster Vaccine - immunology; Humans; Immunoglobulin A - blood; Immunoglobulin G - blood; Immunology; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Lymphocyte Activation - immunology; Middle Aged; middle-aged adults; preexisting immunity; T-cells; Vaccination; Vaccines, Attenuated - immunology; varicella zoster virus; Varicella Zoster Virus Infection - immunology; Varicella Zoster Virus Infection - prevention & control
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.00046

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 (  = 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.