Immunity against conserved epitopes dominates after two consecutive exposures to SARS-CoV-2 Omicron BA.1
Alexander Muik,
Jasmin Quandt,
Bonny Gaby Lui,
Maren Bacher,
Sebastian Lutz,
Maika Grünenthal,
Aras Toker,
Jessica Grosser,
Orkun Ozhelvaci,
Olga Blokhina,
Svetlana Shpyro,
Isabel Vogler,
Nadine Salisch,
Özlem Türeci,
Ugur Sahin
Affiliations
Alexander Muik
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
Jasmin Quandt
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
Bonny Gaby Lui
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
Maren Bacher
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
Sebastian Lutz
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
Maika Grünenthal
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
Olga Blokhina
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
Svetlana Shpyro
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
Isabel Vogler
BioNTech, An der Goldgrube 12, 55131 Mainz, Germany
Nadine Salisch
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: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure histories become increasingly complex through original and variant-adapted vaccines and infections with viral variants. Upon exposure to the highly altered Omicron spike glycoprotein, pre-immunized individuals predominantly mount recall responses of Wuhan-Hu-1 (wild-type)-imprinted memory B (BMEM) cells mostly targeting conserved non-neutralizing epitopes, leading to diminished Omicron neutralization. We investigated the impact of imprinting in individuals double/triple vaccinated with a wild-type-strain-based mRNA vaccine who, thereafter, had two consecutive exposures to Omicron BA.1 spike (breakthrough infection followed by BA.1-adapted vaccine). We found that depletion of conserved epitope-recognizing antibodies using a wild-type spike bait results in strongly diminished BA.1 neutralization. Furthermore, spike-specific BMEM cells recognizing conserved epitopes are much more prevalent than BA.1-specific BMEM cells. Our observations suggest that imprinted BMEM cell recall responses limit the induction of strain-specific responses even after two consecutive BA.1 spike exposures. Vaccine adaptation strategies need to consider that prior SARS-CoV-2 infections and vaccinations may cause persistent immune imprinting.
