Divergent SARS-CoV-2 Omicron–reactive T and B cell responses in COVID-19 vaccine recipients
Corine H. GeurtsvanKessel, Daryl Geers, Katharina S. Schmitz, Anna Z. Mykytyn, Mart M. Lamers, Susanne Bogers, Sandra Scherbeijn, Lennert Gommers, Roos S. G. Sablerolles, Nella N. Nieuwkoop, Laurine C. Rijsbergen, Laura L.A. van Dijk, Janet de Wilde, Kimberley Alblas, Tim I. Breugem, Bart Rijnders, Herbert de Jager, Daniela Weiskopf, P.H.M. van der Kuy, Alessandro Sette, Marion Koopmans, Alba Grifoni, Bart L. Haagmans, Rory D. de Vries
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.