{Reference Type}: Journal Article
{Title}: SARS-CoV-2 breakthrough infections enhance T cell response magnitude, breadth, and epitope repertoire.
{Author}: Tarke A;Ramezani-Rad P;Alves Pereira Neto T;Lee Y;Silva-Moraes V;Goodwin B;Bloom N;Siddiqui L;Avalos L;Frazier A;Zhang Z;da Silva Antunes R;Dan J;Crotty S;Grifoni A;Sette A;
{Journal}: Cell Rep Med
{Volume}: 5
{Issue}: 6
{Year}: 2024 Jun 18
{Factor}: 16.988
{DOI}: 10.1016/j.xcrm.2024.101583
{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.