CMV seropositivity in older adults changes the T cell repertoire, but does not prevent antibody or cellular responses to SARS-CoV-2 vaccination

Abstract Chronic infection with human cytomegalovirus (CMV) may contribute to poor vaccine efficacy in older adults. We assessed effects of CMV serostatus on antibody quantity and quality, as well as cellular memory recall responses, after 2 and 3 SARS-CoV-2 mRNA vaccine doses, in older adults in assisted living facilities. CMV serostatus did not affect anti-Spike and anti-RBD IgG antibody levels, nor neutralization capacity against wildtype or beta variants of SARS-CoV-2 several months after vaccination. CMV seropositivity altered T cell expression of senescence-associated markers and increased T EMRA cell numbers, as has been previously reported; however, this did not impact Spike-specific CD4 + T cell memory recall responses. CMV seropositive individuals did not have a higher incidence of COVID-19, though prior infection influenced humoral immunity. Therefore, CMV seropositivity may alter T cell composition but does not impede the durability of humoral protection or cellular memory responses after SARS-CoV-2 mRNA vaccination in older adults. Key Points CMV seropositive older adults have more EMRA and terminally differentiated T cells CMV seropositivity does not prevent antibody maintenance after SARS-CoV-2 vaccination CMV seropositivity does not impede SARS-CoV-2 vaccine T cell memory recall responses