Divergent SARS-CoV-2 Omicron-reactive T and B cell responses in COVID-19 vaccine recipients

Sci Immunol. 2022 Mar 25;7(69):eabo2202. doi: 10.1126/sciimmunol.abo2202. Epub 2022 Mar 25.

Abstract

The severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is spreading rapidly, even in vaccinated individuals, raising concerns about immune escape. Here, we studied neutralizing antibodies and T cell responses targeting SARS-CoV-2 D614G [wild type (WT)] and the Beta, Delta, and Omicron variants of concern in a cohort of 60 health care workers after immunization with ChAdOx-1 S, Ad26.COV2.S, mRNA-1273, or BNT162b2. High binding antibody levels against WT SARS-CoV-2 spike (S) were detected 28 days after vaccination with both mRNA vaccines (mRNA-1273 or BNT162b2), which substantially decreased after 6 months. In contrast, antibody levels were lower after Ad26.COV2.S vaccination but did not wane. Neutralization assays showed consistent cross-neutralization of the Beta and Delta variants, but neutralization of Omicron was significantly lower or absent. BNT162b2 booster vaccination after either two mRNA-1273 immunizations or Ad26.COV2 priming partially restored neutralization of the Omicron variant, but responses were still up to 17-fold decreased compared with WT. SARS-CoV-2-specific T cells were detected up to 6 months after all vaccination regimens, with more consistent detection of specific CD4+ than CD8+ T cells. No significant differences were detected between WT- and variant-specific CD4+ or CD8+ T cell responses, including Omicron, indicating minimal escape at the T cell level. This study shows that vaccinated individuals retain T cell immunity to the SARS-CoV-2 Omicron variant, potentially balancing the lack of neutralizing antibodies in preventing or limiting severe COVID-19. Booster vaccinations are needed to further restore Omicron cross-neutralization by antibodies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ad26COVS1
  • BNT162 Vaccine
  • CD8-Positive T-Lymphocytes
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Humans
  • SARS-CoV-2*

Substances

  • Ad26COVS1
  • COVID-19 Vaccines
  • BNT162 Vaccine

Supplementary concepts

  • SARS-CoV-2 variants