Progressive loss of conserved spike protein neutralizing antibody sites in Omicron sublineages is balanced by preserved T cell immunity
Alexander Muik,
Bonny Gaby Lui,
Jasmin Quandt,
Huitian Diao,
Yunguan Fu,
Maren Bacher,
Jessica Gordon,
Aras Toker,
Jessica Grosser,
Orkun Ozhelvaci,
Katharina Grikscheit,
Sebastian Hoehl,
Niko Kohmer,
Yaniv Lustig,
Gili Regev-Yochay,
Sandra Ciesek,
Karim Beguir,
Asaf Poran,
Isabel Vogler,
Özlem Türeci,
Ugur Sahin
Affiliations
Alexander Muik
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
Bonny Gaby Lui
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
Jasmin Quandt
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
Huitian Diao
BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA
Yunguan Fu
InstaDeep, Ltd., 5 Merchant Square, London W2 1AY, UK
Maren Bacher
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
Jessica Gordon
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
Aras Toker
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
Jessica Grosser
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
Orkun Ozhelvaci
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
Katharina Grikscheit
Institute for Medical Virology, University Hospital, Goethe University Frankfurt, 60596 Frankfurt am Main, Germany
Sebastian Hoehl
Institute for Medical Virology, University Hospital, Goethe University Frankfurt, 60596 Frankfurt am Main, Germany
Niko Kohmer
Institute for Medical Virology, University Hospital, Goethe University Frankfurt, 60596 Frankfurt am Main, Germany
Yaniv Lustig
Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel; Central Virology Laboratory, Public Health Services, Ministry of Health, Tel-Hashomer, Ramat Gan, Israel
Gili Regev-Yochay
Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel; SPRI-Sheba Pandemic Preparedness Research Institute, Sheba Medical Center Tel Hashomer, Ramat Gan, Israel
Sandra Ciesek
Institute for Medical Virology, University Hospital, Goethe University Frankfurt, 60596 Frankfurt am Main, Germany; DZIF – German Centre for Infection Research, External Partner Site, 60596 Frankfurt am Main, Germany
Karim Beguir
InstaDeep, Ltd., 5 Merchant Square, London W2 1AY, UK
Asaf Poran
BioNTech US, 40 Erie Street, Cambridge, MA 02139, USA
Isabel Vogler
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
Özlem Türeci
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany; HI-TRON – Helmholtz Institute for Translational Oncology Mainz by DKFZ, Obere Zahlbacherstr. 63, 55131 Mainz, Germany
Ugur Sahin
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany; TRON gGmbH – Translational Oncology at the University Medical Center of the Johannes Gutenberg University, Freiligrathstraße 12, 55131 Mainz, Germany; Corresponding author
Summary: Evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has led to the emergence of sublineages with different patterns of neutralizing antibody evasion. We report that Omicron BA.4/BA.5 breakthrough infection of individuals immunized with SARS-CoV-2 wild-type-strain-based mRNA vaccines results in a boost of Omicron BA.4.6, BF.7, BQ.1.1, and BA.2.75 neutralization but does not efficiently boost BA.2.75.2, XBB, or XBB.1.5 neutralization. In silico analyses showed that the Omicron spike glycoprotein lost most neutralizing B cell epitopes, especially in sublineages BA.2.75.2, XBB, and XBB.1.5. In contrast, T cell epitopes are conserved across variants including XBB.1.5. T cell responses of mRNA-vaccinated, SARS-CoV-2-naive individuals against the wild-type strain, Omicron BA.1, and BA.4/BA.5 were comparable, suggesting that T cell immunity against recent sublineages including XBB.1.5 may remain largely unaffected. While some Omicron sublineages effectively evade B cell immunity, spike-protein-specific T cell immunity, due to the nature of polymorphic cell-mediated immune responses, may continue to contribute to prevention/limitation of severe COVID-19 manifestation.
