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Cell Rep Med . SARS-CoV-2 breakthrough infections enhance T cell response magnitude, breadth, and epitope repertoire

tetano

Editor, Senior Moderator
Cell Rep Med


. 2024 May 17:101583.
doi: 10.1016/j.xcrm.2024.101583. Online ahead of print. SARS-CoV-2 breakthrough infections enhance T cell response magnitude, breadth, and epitope repertoire

Alison Tarke[SUP] 1 [/SUP], Parham Ramezani-Rad[SUP] 1 [/SUP], Tertuliano Alves Pereira Neto[SUP] 1 [/SUP], Yeji Lee[SUP] 1 [/SUP], Vanessa Silva-Moraes[SUP] 2 [/SUP], Benjamin Goodwin[SUP] 1 [/SUP], Nathaniel Bloom[SUP] 1 [/SUP], Leila Siddiqui[SUP] 1 [/SUP], Liliana Avalos[SUP] 1 [/SUP], April Frazier[SUP] 1 [/SUP], Zeli Zhang[SUP] 1 [/SUP], Ricardo da Silva Antunes[SUP] 1 [/SUP], Jennifer Dan[SUP] 3 [/SUP], Shane Crotty[SUP] 4 [/SUP], Alba Grifoni[SUP] 5 [/SUP], Alessandro Sette[SUP] 6 [/SUP]



Affiliations
Abstract

Little is known about the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or SARS2) vaccine breakthrough infections (BTIs) on the magnitude and breadth of the T cell repertoire after exposure to different variants. We studied samples from individuals who experienced symptomatic BTIs during Delta or Omicron waves. In the pre-BTI samples, 30% of the donors exhibited substantial immune memory against non-S (spike) SARS2 antigens, consistent with previous undiagnosed asymptomatic SARS2 infections. Following symptomatic BTI, we observed (1) enhanced S-specific CD4 and CD8 T cell responses in donors without previous asymptomatic infection, (2) expansion of CD4 and CD8 T cell responses to non-S targets (M, N, and nsps) independent of SARS2 variant, and (3) generation of novel epitopes recognizing variant-specific mutations. These variant-specific T cell responses accounted for 9%-15% of the total epitope repertoire. Overall, BTIs boost vaccine-induced immune responses by increasing the magnitude and by broadening the repertoire of T cell antigens and epitopes recognized.

Keywords: B cells; COVID-19 vaccination; Delta; Omicron; SARS-CoV-2; T cells; breakthrough infection; coronavirus; de novo responses.

 
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