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.

Previous studies have shown that certain vaccines induce suboptimal responses in people living with HIV (PLWH). However, responses to SARS-CoV-2 vaccines have not been fully characterized in these patients. Here we show that the BNT162b2 vaccine induces robust immune responses comparable to responses in healthy donors.

BACKGROUND. T cell responses to the common cold coronaviruses have not been well characterized. Preexisting T cell immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported, and a recent study suggested that this immunity was due to cross-recognition of the novel coronavirus by T cells specific for the common cold coronaviruses. METHODS. We used the enzyme-linked immunospot (ELISPOT) assay to characterize the T cell responses against peptide pools derived from the spike protein of 3 common cold coronaviruses (HCoV-229E, HCoV-NL63, and HCoV-OC43) and SARS-CoV-2 in 21 healthy donors (HDs) who were seronegative for SARS-CoV-2 and had no known exposure to the virus. An in vitro expansion culture assay was also used to analyze memory T cell responses. RESULTS. We found responses to the spike protein of the 3 common cold coronaviruses in many of the donors. We then focused on HCoV-NL63 and detected broad T cell responses to the spike protein and identified 22 targeted peptides. Interestingly, only 1 study participant had a significant response to SARS-CoV-2 spike or nucleocapsid protein in the ELISPOT assay. In vitro expansion studies suggested that T cells specific for the HCoV-NL63 spike protein in this individual could also recognize SARS-CoV-2 spike protein peptide pools. CONCLUSION. HDs have circulating T cells specific for the spike proteins of HCoV-NL63, HCoV-229E, and HCoV-OC43. T cell responses to SARS-CoV-2 spike and nucleocapsid proteins were present in only 1 participant and were potentially the result of cross-recognition by T cells specific for the common cold coronaviruses. Further studies are needed to determine whether this cross-recognition influences coronavirus disease 2019 (COVID-19) outcomes.

CONFLICTS OF INTERESTDMP and KNS have filed for patent protection on a subset of the technologies described herein (US provisional patent application no. 62/407,820). AD, ALC, FD, DMP, JB, and KNS have filed for patent protection on a subset of the technologies described herein (US provisional patent application no. 63/135,534). SZ is a founder of, holds equity in, and serves as a consultant to Personal Genome Diagnostics. SZ holds equity in Thrive Earlier

Little is known about the decay kinetics of COVID-19 vaccine-elicited SARS-CoV-2 specific T cells. In this study we show a modest decline in the frequency of these T cells at 6 months and demonstrate robust expansion in response to antigen and recognition of spike peptides from the delta variant.

Elite controllers are HIV-1 positive subjects who control viral replication without antiretroviral therapy. Many of these subjects have replication-competent virus and thus represent a model of a functional cure. Peripheral CD4+ T cells in these subjects have small reservoirs with a low frequency of intact proviruses. Furthermore, recent studies suggest that many of these intact proviruses are disproportionally integrated at sites that have limited transcriptional activity raising the possibility that replication-competent viruses do not replicate because they are in a “blocked and locked” state. However, this feature is probably a consequence rather than a cause of elite control. Additionally, evolution of plasma virus has been detected in many elites suggesting that there continues to be ongoing viral replication in other compartments. While exceptional elite controllers with very limited viral reservoirs have recently been described, more work is needed to determine whether these patients have achieved a sterilizing cure.

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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.