AS01-adjuvanted vaccine alters baseline correlates of T cell response to varicella zoster virus in older adults

The recombinant zoster vaccine (RZV), which uses the AS01 adjuvant system, confers more than 90 % efficacy in older adults against herpes zoster. While most older adults have been exposed to chickenpox, it remains unclear why a two-dose schedule is needed to boost an anamnestic response in the older adults. We evaluated the baseline and post-vaccination gene expression, cytokine and vaccine immunogenicity in healthy older adults aged 50–65 years old with a known history of varicella zoster. All participants developed strong humoral responses after the first vaccine dose. In contrast, the first dose elicited heterogeneous T cell responses, which were significantly boosted after the second dose. Participants who elicited greater T cell responses to the first dose had distinct baseline gene expression profiles compared to those who induced protective T cell levels only after receiving two doses. Moreover, based on a gene set that was predictive of the magnitude of protective T cell responses, we showed that the first vaccine dose altered the baseline expression of these genes. Together, the results indicate that RZV can alter the baseline state of immune cells to boost cellular immune responses to the second dose, offering potential strategies for improving vaccine efficacy in older adults. • Despite prevalent VZV immunity in older adults, two doses of recombinant zoster vaccine are needed to confer protection. • Two doses of recombinant zoster vaccine are needed to elicit protective T cell responses in most older adults. • The first dose of recombinant zoster vaccine can alter baseline gene expression, improvingT cell responses after the second dose.