CD4+ T cells from COVID-19 mRNA vaccine recipients recognize a conserved epitope present in diverse coronaviruses

Abstract

Recent studies have shown that vaccinated individuals harbor T cells that can cross-recognize SARS-CoV-2 and endemic human common cold coronaviruses (HCoVs). However, it is still unknown whether CD4+ T cells from vaccinated individuals recognize peptides from bat coronaviruses that may have the potential of causing future pandemics. In this study, we identified a SARS-CoV-2 spike protein epitope (S815-827) that is conserved in coronaviruses from different genera and subgenera including SARS-CoV, MERS-CoV, multiple bat coronaviruses and a feline coronavirus. Our results showed that S815-827 is recognized by 42% of vaccinated participants in our study who received the Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) COVID-19 vaccines. Using T cell expansion and T cell receptor sequencing assays, we demonstrated that S815-827-reactive CD4+ T cells from the majority of responders cross-recognize homologous peptides from at least 6 other diverse coronaviruses. Our results support the hypothesis that the current mRNA vaccines elicit T cell responses that can cross-recognize bat coronaviruses, and thus might induce some protection against potential zoonotic outbreaks. Furthermore, our data provide important insights that inform the development of T cell-based pan-coronavirus vaccine strategies.

Immunological memory to Common Cold Coronaviruses assessed longitudinally over a three-year period

“…Understanding the steady state dynamics of CCC antibody and T cell responses in humans is of potential relevance in the context of the long-term evolution of the SARS-CoV-2 pandemic, in the context of the current scenario, where a large fraction of the human population is exposed and/or vaccinated. Furthermore, it has been widely reported that CCC T cell responses are associated with some degree of cross-reactivity with SARS-CoV-2, and that this cross-reactivity can at least in part explain the pre-existing T cell memory reactivity recognizing SARS-CoV-2 sequences, observed in SARS-CoV-2 unexposed subjects [25][26][27][28][29] . A putative role for CCC cross-reactive T cells in modulating COVID-19 vaccination and disease outcomes has been indicated by several independent studies 26,[30][31][32][33] .…”

“…Furthermore, it has been widely reported that CCC T cell responses are associated with some degree of cross-reactivity with SARS-CoV-2, and that this cross-reactivity can at least in part explain the pre-existing T cell memory reactivity recognizing SARS-CoV-2 sequences, observed in SARS-CoV-2 unexposed subjects 25–29 . A putative role for CCC cross-reactive T cells in modulating COVID-19 vaccination and disease outcomes has been indicated by several independent studies 26,30–33 .…”

The prospect of universal coronavirus immunity: a characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and common human coronaviruses

“…In parallel, we studied reactivity against the endemic hCoV, observing immune responses in the majority of healthy and immunocompromised subjects. Interestingly, COVID-19 survivors displayed a broader reactivity pattern against the endemic viruses, suggesting possible induction of cross-reactive immunity upon resolution of COVID-19 that is increasingly recognized in literature[56, 57]. Ex vivo expanded T cells specific for SARS-CoV2 S, M and NP antigens and the equivalent antigens from hCoVs were further tested for cross-reactivity.…”

Immune Senescence Markers Predict the Cellular Immune Response to BNT162b2 Vaccination in Hemodialysis Patients

“…Both markers indicate that a lower proportion of naive CD4 T cells responds to the vaccine antigen. Indeed, animal and human studies show that mRNA vaccines induce strong CD4 T-cell responses [ 20 , 21 ]. Not unsurprisingly, these markers of T-cell aging did not predict the humoral response.…”