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

Jergovic, M.; Uhrlaub, J. L.; Watanabe, M.; Bradshaw, C. M.; White, L. M.; LaFleur, B. J.; Edwards, T.; Sprissler, R.; Worobey, M.; Bhattacharya, D.; Nikolich-Zugich, J.

doi:10.1101/2021.07.22.453287

bioRxiv · 10.1101/2021.07.22.453287

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

Jergovic, M.·Uhrlaub, J. L.·Watanabe, M.·Bradshaw, C. M.·White, L. M.·LaFleur, B. J.·Edwards, T.·Sprissler, R.·Worobey, M.·Bhattacharya, D.·Nikolich-Zugich, J.

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Abstract

Aging is associated with a reduced magnitude of primary immune responses to vaccination and constriction of immune receptor repertoire diversity. Clinical trials demonstrated 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 in <50 and >55 age cohorts of mRNA vaccine recipients. We have further measured neutralizing antibody titers for B.1.617.1 (Kappa) and B.1.595; a SARS-CoV-2 isolate bearing Spike mutation E484Q. As reported, robust immunity required the second dose of vaccine. Older vaccinees manifested robust cellular immunity against early-pandemic SARS-CoV-2 and more recent variants, which remained statistically comparable to the adult group. The older cohort had lower neutralizing capacity at the first time point following the second dose, but at later time points immunity was indistinguishable between them. 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 summaryVaccine 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 O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=73 SRC="FIGDIR/small/453287v2_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@1091655org.highwire.dtl.DTLVardef@1996173org.highwire.dtl.DTLVardef@ccf2f9org.highwire.dtl.DTLVardef@163ed22_HPS_FORMAT_FIGEXP M_FIG C_FIG Created with BioRender.com

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Jergovic, M., Uhrlaub, J. L., Watanabe, M., Bradshaw, C. M., White, L. M., LaFleur, B. J., Edwards, T., Sprissler, R., Worobey, M., Bhattacharya, D., Nikolich-Zugich, J.. 2021-07-22. Competent immune responses to SARS-CoV-2 variants in older adults following mRNA vaccination. https://doi.org/10.1101/2021.07.22.453287

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