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Immunosenescence may impact the functionality and breadth of vaccine-elicited humoral immune responses. The ability of sera to neutralize the SARS-CoV-2 spike protein (S) from Beta, Gamma, Delta, and Epsilon variants of concern (VOCs) relative to the ancestral Wuhan-Hu-1 strain was compared in Comirnaty COVID-19-vaccinated elderly nursing home residents, either SARS-CoV-2 naïve (n = 22) or experienced (n = 8), or SARS-CoV-2 naïve younger individuals (n = 18) and non-vaccinated individuals who recovered from severe COVID-19 (n = 19). In all groups, except that including SARS-CoV-2-experienced nursing home residents, some participants lacked NtAb against one or more VOCs, mainly the Beta variant (15–20%). Serum NtAb titers were lowest against the Beta variant followed by Gamma, Delta and Epsilon variants. Overall, fold change reduction in NtAb titers relative to the ancestral strain was greatest for the Beta variant (6.7–19.4) followed by Gamma (4.8–16.0), Epsilon (2.9–13.4), and Delta (3.5–6.5) variants, although subtle differences were observed for Beta, Epsilon and Delta variants across comparison groups. In summary, older age, frailty, and concurrence of co-morbidities had no major impact on the serum NtAb activity profile against SARS-CoV-2 VOCs.
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