SARS-CoV-2 mRNA vaccines induce broad CD4+ T cell responses that recognize SARS-CoV-2 variants and HCoV-NL63
Open accessAbstract
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 (CCCs) remains unknown. In this study, we analyzed CD4+ T cell responses to spike peptides from SARS-CoV-2 and 3 CCCs (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 showed broad T cell responses to the SARS-CoV-2 spike protein, and we identified 23 distinct targeted peptides in 9 participants, including 1 peptide that was targeted in 6 individuals. Only 4 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 they recognized the spike protein from the ancestral virus. Interestingly, we observed a 3-fold increase in the CD4+ T cell responses to HCoV-NL63 spike peptides after 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 against some endemic coronaviruses.
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Memory CD4+ and CD8+ T cells specific for antigen are probably less vulnerable to antibody escape mutations in viral variants because T cells can recognize epitopes across the Spike protein.
“antigen-specific memory CD4+ and CD8+ T cells are likely to be less affected by antibody escape mutations in variant viral strains, as T cells can recognize peptide epitopes distributed throughout the SARS-CoV-2 Spike protein (Angyal et al., 2021; Tarke et al., 2021b; Woldemeskel et al., 2021).”
From Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination (2021) · cites this paper as Woldemeskel et al., 2021
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- Authors
- Woldemeskel, B. A., Garliss, C. C., & Blankson, J. N.
- Corresponding author
- Blankson, Joel N.
- ORCID
- Blankson, Joel N.
- Venue
- Journal of Clinical Investigation
- Published
- 2021-05-17
- Volume
- 131
- Issue
- 10
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC8121504
- OpenAlex
- W3141087105
- Cited by
- 175
- References
- 39
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 16 · 2023: 24 · 2022: 72 · 2021: 47
- FWCI
- 12.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH (R01AI120024)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- COVID-19 mRNA vaccine, BNT162b2, mRNA-1273, CD4+ T cell responses, common cold coronaviruses, HCoV-NL63, HCoV-229E, HCoV-OC43, SARS-CoV-2 variants, Alpha variant, Beta variant, cross-protection, vaccine-induced immunity
- MeSH terms
- SARS-CoV-2, COVID-19 Vaccines, BNT162 Vaccine, Adult, Cross Reactions, Female, Humans, Male, Middle Aged, RNA, Messenger, CD4-Positive T-Lymphocytes, Coronavirus 229E, Human, Coronavirus OC43, Human, Coronavirus NL63, Human, Spike Glycoprotein, Coronavirus
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