Age-related differences in immune responses to inactivated influenza and adjuvanted recombinant herpes zoster vaccines

Gizem Kilic; Esther J.M. Taks; Leonie S. Helder; Elisabeth A. Dulfer; Büsra Geckin; Liesbeth van Emst; Heidi Lemmers; Stefano Berrè; Adhidev Biswas; Mumin Ozturk; Yutaka Negishi; Wivine Burny; Sofia Maria Buonocore; Jaap ten Oever; Musa M. Mhlanga; Mihai G. Netea

doi:10.1172/jci.insight.195618

Age-related differences in immune responses to inactivated influenza and adjuvanted recombinant herpes zoster vaccines

Gizem Kilic,¹ Esther J.M. Taks,¹ Leonie S. Helder,¹ Elisabeth A. Dulfer,¹ Büsra Geckin,¹ Liesbeth van Emst,¹ Heidi Lemmers,¹ Stefano Berrè,² Adhidev Biswas,² Mumin Ozturk,⁴ Yutaka Negishi,⁴ Wivine Burny,² Sofia Maria Buonocore,² Jaap ten Oever,¹ Musa M. Mhlanga,⁴ and Mihai G. Netea¹

Published June 2, 2026 - More info

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Abstract

Immunosenescence, the biological aging of the immune system, leads to dysregulated immune responses, increasing susceptibility to infections and reducing vaccine efficacy in older adults, as seen with flu vaccines. In contrast, the AS01-adjuvanted recombinant herpes zoster vaccine (RZV) maintains high and sustained efficacy, offering 82% protection against herpes zoster at 11-years post-vaccination, in individuals over 50. To identify factors impacting age-dependent vaccine efficacy, we conducted a randomized, partially placebo-controlled clinical study. Young adults (18-35 years, n=84) were randomized 3:3:1:1 to receive either RZV, an inactivated quadrivalent seasonal influenza vaccine (IIV4), placebo for RZV or placebo for IIV4, while older adults (≥60, n=63) were randomized 1:1 to receive RZV or IIV4. RZV elicited robust antibody production, antigen-specific polyfunctional CD4+ T cell responses and IFN-γ from PBMCs in both age groups, while IIV4 increased antibody responses, but induced fewer antigen-specific CD4+ T cells and no elevation of IFN-γ from PBMCs. Interestingly, RZV reduced systemic inflammation in older adults, particularly after the second injection. Baseline inflammation negatively correlated with antibody production and IFN-γ response, especially after RZV. Our findings suggest that RZV may help overcome immunosenescence by enhancing cellular responses and potentially decreasing systemic inflammation, deserving further investigation into the underlying molecular mechanisms.

Age-related differences in immune responses to inactivated influenza and adjuvanted recombinant herpes zoster vaccines

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Age-related differences in immune responses to inactivated influenza and adjuvanted recombinant herpes zoster vaccines

Gizem Kilic,1 Esther J.M. Taks,1 Leonie S. Helder,1 Elisabeth A. Dulfer,1 Büsra Geckin,1 Liesbeth van Emst,1 Heidi Lemmers,1 Stefano Berrè,2 Adhidev Biswas,2 Mumin Ozturk,4 Yutaka Negishi,4 Wivine Burny,2 Sofia Maria Buonocore,2 Jaap ten Oever,1 Musa M. Mhlanga,4 and Mihai G. Netea1

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