Impact of Previous Common Human Coronavirus Exposure on SARS-CoV-2-Specific T-Cell and Memory B-Cell Response after mRNA-Based Vaccination

Viruses. 2023 Feb 24;15(3):627. doi: 10.3390/v15030627.

Abstract

Objective: T-cell responses against SARS-CoV-2 are observed in unexposed individuals, attributed to previous common human coronavirus (HCoV) infections. We evaluated the evolution of this T-cell cross-reactive response and the specific memory B-cells (MBCs) after the SARS-CoV-2 mRNA-based vaccination and its impact on incident SARS-CoV-2 infections.

Methods: This was a longitudinal study of 149 healthcare workers (HCWs) that included 85 unexposed individuals that were subdivided according to previous T-cell cross-reactivity, who were compared to 64 convalescent HCWs. Changes in specific T-cell response and memory B-cell (MBC) levels were compared at baseline and after two doses of the SARS-CoV-2 mRNA-based vaccine.

Results: A cross-reactive T-cell response was found in 59% of unexposed individuals before vaccination. Antibodies against HKU1 positively correlated with OC43 and 229E antibodies. Spike-specific MBCs was scarce in unexposed HCWs regardless of the presence of baseline T-cell cross-reactivity. After vaccination, 92% and 96% of unexposed HCWs with cross-reactive T-cells had CD4+ and CD8+ T-cell responses to the spike protein, respectively. Similar results to that were found in convalescents (83% and 92%, respectively). Contrarily, higher than that which was observed in unexposed individuals without T-cell cross-reactivity showed lower CD4+ and CD8+ T-cell responses (73% in both cases, p = 0.03). Nevertheless, previous cross-reactive T-cell response was not associated with higher levels of MBCs after vaccination in unexposed HCWs. During a follow-up of 434 days (IQR, 339-495) after vaccination, 49 HCWs (33%) became infected, with a significant positive correlation between spike-specific MBC levels and isotypes IgG+ and IgA+ after vaccination and a longer time to get infected. Interestingly, T-cell cross-reactivity did not reduce the time to vaccine breakthrough infections.

Conclusion: While pre-existing T-cell cross-reactivity enhances the T-cell response after vaccination, it does not increase SARS-CoV-2-specific MBC levels in the absence of previous infection. Overall, the level of specific MBCs determines the time to breakthrough infections, regardless of the presence of T-cell cross-reactivity.

Keywords: SARS-CoV-2; coronavirus; cross-reactive; mRNA vaccine; memory B-cells.

MeSH terms

  • Antibodies
  • Antibodies, Viral
  • Breakthrough Infections
  • COVID-19* / prevention & control
  • Humans
  • Longitudinal Studies
  • RNA, Messenger
  • SARS-CoV-2* / genetics
  • Spike Glycoprotein, Coronavirus / genetics
  • Vaccination

Substances

  • Antibodies
  • RNA, Messenger
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Grants and funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Only intra-departmental funds were granted for this study.