1. Immunity against conserved epitopes dominates after two consecutive exposures to SARS-CoV-2 Omicron BA.1.
- Author
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Muik A, Quandt J, Lui BG, Bacher M, Lutz S, Grünenthal M, Toker A, Grosser J, Ozhelvaci O, Blokhina O, Shpyro S, Vogler I, Salisch N, Türeci Ö, and Sahin U
- Subjects
- Humans, COVID-19 Vaccines immunology, Epitopes immunology, Female, Middle Aged, Adult, Male, Memory B Cells immunology, SARS-CoV-2 immunology, COVID-19 immunology, COVID-19 virology, Spike Glycoprotein, Coronavirus immunology, Antibodies, Viral immunology, Antibodies, Neutralizing immunology
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure histories become increasingly complex through original and variant-adapted vaccines and infections with viral variants. Upon exposure to the highly altered Omicron spike glycoprotein, pre-immunized individuals predominantly mount recall responses of Wuhan-Hu-1 (wild-type)-imprinted memory B (B
MEM ) cells mostly targeting conserved non-neutralizing epitopes, leading to diminished Omicron neutralization. We investigated the impact of imprinting in individuals double/triple vaccinated with a wild-type-strain-based mRNA vaccine who, thereafter, had two consecutive exposures to Omicron BA.1 spike (breakthrough infection followed by BA.1-adapted vaccine). We found that depletion of conserved epitope-recognizing antibodies using a wild-type spike bait results in strongly diminished BA.1 neutralization. Furthermore, spike-specific BMEM cells recognizing conserved epitopes are much more prevalent than BA.1-specific BMEM cells. Our observations suggest that imprinted BMEM cell recall responses limit the induction of strain-specific responses even after two consecutive BA.1 spike exposures. Vaccine adaptation strategies need to consider that prior SARS-CoV-2 infections and vaccinations may cause persistent immune imprinting., Competing Interests: Declaration of interests U.S. and O.T. are management board members and employees at BioNTech SE. A.M., B.G.L., J.Q., M.B., S.L., M.G., A.T., J.G., I.V., O.B., S.S., N.S., and O.O. are employees at BioNTech SE. U.S., O.T., and A.M. are inventors on patents and patent applications related to RNA technology and COVID-19 vaccines. U.S., O.T., A.M., B.G.L., J.Q., M.B., S.L., A.T., M.G., J.G., I.V., O.B., S.S., N.S., and O.O. have securities from BioNTech SE., (Copyright © 2024. Published by Elsevier Inc.)- Published
- 2024
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