Competent immune responses to SARS-CoV-2 variants in older adults following mRNA vaccination

Jergovič, Mladen; Uhrlaub, Jennifer L.; Watanabe, Makiko; Bradshaw, Christine M.; White, Lisa M.; LaFleur, Bonnie J.; Edwards, Taylor; Sprissler, Ryan; Worobey, Michael; Bhattacharya, Deepta; Nikolich-Žugich, Janko

Aging is associated with a reduced magnitude of primary immune responses to vaccination and constriction of immune receptor repertoire diversity. Clinical trials demonstrate high efficacy of mRNA based SARS-CoV-2 vaccines in older adults but concerns about virus variant escape have not been well addressed. We have conducted an in-depth analysis of humoral and cellular immunity against an early-pandemic viral isolate and compared that to the P.1. (Gamma) and B.1.617.2 (Delta) variants, as well to a B.1.595 SARS-CoV-2 isolate bearing Spike mutation E484Q, in <55 and >65 age cohorts of mRNA vaccine recipients. As reported, robust immunity required the second dose of vaccine. Older vaccine recipients exhibited an expected 3-5x reduction (but not a complete loss) in neutralizing antibody titers against both P.1. (Gamma) and the B.1.595 virus at the peak of the boosted response. However, older vaccinees manifest robust cellular immunity against early-pandemic SARS-CoV-2 and more recent variants, which remained statistically comparable to the adult group. While the duration of these immune responses remains to be determined over longer periods of time, these results provide reasons for optimism regarding vaccine protection of older adults against SARS-CoV-2 variants and inform thinking about boost vaccination with variant vaccines. eTOC summary Vaccine responses are often diminished with aging, but we found strong responses to SARS-CoV-2 in older adults following mRNA vaccination. T cell responses were not diminished when confronted by SARS-CoV-2 variants. Neutralizing Ab were reduced but not more than those in adults. Graphical Abstract Created with BioRender.com