SARS-CoV-2 mRNA vaccines induce broad CD4+ T cell responses that recognize SARS-CoV-2 variants and HCoV-NL63

Abstract

Recent studies have shown T cell cross-recognition of SARS-CoV-2 and common cold coronavirus spike proteins. However, the effect of SARS-CoV-2 vaccines on T cell responses to common cold coronaviruses remain unknown. In this study, we analyzed CD4+ T cell responses to spike peptides from SARS-CoV-2 and 3 common cold coronaviruses (HCoV-229E, HCoV-NL63, and HCoV-OC43) before and after study participants received Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) mRNA-based COVID-19 vaccines. Vaccine recipients made broad T cell responses to the SARS-CoV-2 spike protein and we identified 23 distinct targeted peptides in 9 participants including one peptide that was targeted by 6 individuals. Only 4 out of these 23 targeted peptides would potentially be affected by mutations in the UK (B.1.1.7) and South African (B.1.351) variants and CD4+ T cells from vaccine recipients recognized the 2 variant spike proteins as effectively as the spike protein from the ancestral virus. Interestingly, we saw a 3-fold increase in the CD4+ T cell responses to HCoV-NL63 spike peptides post-vaccination. Our results suggest that T cell responses elicited or enhanced by SARS-CoV-2 mRNA vaccines may be able to control SARS-CoV-2 variants and lead to cross-protection from some endemic coronaviruses.

SARS -CoV-2 T-cell immunity to variants of concern following vaccination

“…Considering these variants may escape antibody neutralization, how they influence the T-cell immune response is of particular interest. One published report measured CD4 T-cell vaccine responses to a subset of the mutations in the B.1.1.7 and B.1.351 variants in one of two spike protein subunits, finding no decreased response to variant relative to wild type proteins 45 . However, as the authors acknowledge, wild type responses were very low due to the use of whole proteins rather than peptide pools 45 , which precludes an accurate fold-change assessment.…”

“…One published report measured CD4 T-cell vaccine responses to a subset of the mutations in the B.1.1.7 and B.1.351 variants in one of two spike protein subunits, finding no decreased response to variant relative to wild type proteins 45 . However, as the authors acknowledge, wild type responses were very low due to the use of whole proteins rather than peptide pools 45 , which precludes an accurate fold-change assessment. To determine the impact of these variants on the magnitude of the anti-spike T-cell response in vaccinated individuals, we used our ELISpot assay to stimulate PBMC from vaccinated individuals post-V2 with spike peptide pools from the B.1.1.7, B.1.315, and B1.1.248 SARS-CoV-2 variants ( Figure 4A ).…”

“…Considering these variants may escape antibody neutralization, how they influence the T-cell immune response is of particular interest. One published report measured CD4 T-cell vaccine responses to a subset of the mutations in the B.1.1.7 and B.1.351 variants in one of two spike protein subunits, finding no decreased response to variant relative to wild type proteins 45 .…”

“…However, as the authors acknowledge, wild type responses were very low due to the use of whole proteins rather than peptide pools 45 , which precludes an accurate fold-change assessment. To determine the impact of these variants on the magnitude of the anti-spike T-cell response in vaccinated individuals, we used our ELISpot assay to stimulate PBMC from vaccinated individuals post-V2 with spike peptide pools from the B.1.1.7, B.1.315, and B1.1.248 SARS-CoV-2 variants (Figure 4A).…”

Rapid determination of the wide dynamic range of SARS-CoV-2 Spike T cell responses in whole blood of vaccinated and naturally infected

“…Whole blood CRA and ELISPOT also showed that the region 501-705 AA contained in Pool 4 is the least immunogenic with only 1 out of the 6 vaccine recipients displaying a response at different time points (Figure 3B and C). Interestingly, analysis of individuals who recovered from SARS-CoV-2 infection (23) and in mRNA vaccine recipients (24) showed a similar reduced frequency of response in the Spike region 500-700 AA for CD4 T cells assayed through AIM detection. Taken together, these data show that direct analysis of cytokines secreted in whole blood pulsed with different peptides constitute a reliable method to gauge the presence and magnitude of functional T cells specific for epitopes covered by the utilized peptides.…”