SARS-CoV-2 mRNA Vaccines Induce Broad CD4+ T cell Responses that Recognize SARS-CoV-2 Variants and HCoV-NL63

Abstract

In this study, researchers analyzed the CD4+ T-cell responses to spike peptides from severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 and 3 common cold coronaviruses (CCCs) before and after vaccination with Pfizer or Moderna messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines to determine if the vaccine may be able to confer a T-cell response to SARS-CoV-2 variants and some endemic CCCs.Study participants included 30 healthy individuals who had not tested positive for COVID-19. They were vaccinated with either the Pfizer-BioNTech (BN162b2) or Moderna (MrNA-1273) mRNA COVID-19 vaccines. Some experiments were performed on smaller numbers of subjects for whom sufficient numbers of cells were available.Blood samples were studied to compare and quantify the frequency of virus-specific T cells before and after vaccination. Virus-specific T-cell responses to 3 CCCs (human coronavirus 229E, human coronavirus NL63 (HCoV-NL63), and human coronavirus OC43) were compared before and after vaccination. In the study, the researchers also compared antigen-specific T-cell responses of spike peptides from HCoV-NL63 and SARS-CoV-2. Finally, individual spike peptides targeted by CD4+ T cells were mapped and assayed so that distinct target peptides could be identified. The authors then determined if these spike peptide motifs were present in various coronaviruses, including 2 known COVID-19 variants: UK (B.1.1.7) and South African (B.1.351).The vaccines elicited a strong T-cell response against SARS-CoV-2, with a 74-fold increase in spot-forming units after vaccination. There was also an observed increase in T-cell response to HCoV-NL63, with a 3-fold increase in spot-forming units after vaccination. The results were similar when comparing the T-cell response to specific spike peptides of SARS-CoV-2 and HCoV-NL63 after vaccination: a 15-fold and 6.75-fold increase, respectively, in T cells coexpressing interferon γ and tumor necrosis factor α. Finally, the authors mapped 23 distinct peptides targeted by CD4+ T cells, one of which was conserved in many coronaviruses, including the ancestral COVID-19 virus and the B.1.1.7 and B.1.351 variants.The Pfizer-BioNTech (BN162b2) and Moderna (MrNA-1273) mRNA COVID-19 vaccines elicit strong T-cell responses to SARS-CoV-2. The vaccines elicited a significant increase in the response to HCoV-NL63, a common cold coronavirus, as well. The data, overall, suggest that the mRNA vaccines may provide protection against SARS-CoV-2 as well as some other common cold coronaviruses. The data also suggest that vaccine-elicited CD4+ T cells should recognize some of the widely circulating COVID-19 variants.With this study, the authors offer insight into the protection offered by the Pfizer and Moderna COVID-19 mRNA vaccines against COVID-19, its variants, and possibly common cold coronaviruses. This is important for the general pediatrician to understand as more children become eligible for vaccination against COVID-19. Therefore, it may be reasonable to educate parents on the positive implications of vaccination against COVID-19 and how vaccination may confer crossprotection against some COVID-19 variants and some common cold viruses.