Age differentially affects the maintenance of adaptive immune responses induced by adenoviral versus mRNA vaccines against COVID-19

Abstract Adenoviral and mRNA vaccines encoding the viral spike protein have been deployed globally to contain SARS-CoV-2. Elderly individuals are particularly vulnerable to severe infection, likely reflecting age-related changes in the immune system, which can also compromise vaccine efficacy. It has nonetheless remained unclear to what extent different vaccine platforms are impacted by immunosenescence. Here, we evaluated spike-specific immune responses elicited by vaccination with two doses of BNT162b2 or ChAdOx1-S and subsequently boosted with a single dose of BNT162b2 or mRNA-1273, comparing age-stratified participants with no evidence of prior infection with SARS-CoV-2. We found that ageing profoundly affected the durability of humoral responses and further limited spike-specific CD4 + T cell immunity as a function of progressive erosion of the naive lymphocyte pool in individuals vaccinated initially with BNT162b2, such that protective immunological memory was best maintained in the elderly after primary vaccination with ChAdOx1-S and subsequent boosting with BNT162b2 or mRNA-1273.