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Muik, Alexander; Lui, Bonny Gaby; Bacher, Maren; Wallisch, Ann-Kathrin; Toker, Aras; Couto, Carla Iris Cadima; Güler, Alptekin; Mampilli, Veena; Schmitt, Geneva J; Mottl, Jonathan; Ziegenhals, Thomas; Fesser, Stephanie; Reinholz, Jonas; Wernig, Florian; Schraut, Karla-Gerlinde; Hefesha, Hossam; Cai, Hui; Yang, Qi; Walzer, Kerstin C; Grosser, Jessica; Strauss, Stefan; Finlayson, Andrew; Krüger, Kimberly; Ozhelvaci, Orkun; Grikscheit, Katharina; Kohmer, Niko; Ciesek, Sandra; Swanson, Kena A; Vogel, Annette B; Türeci, Özlem; Sahin, Ugur
Science immunology, 12/2022, Letnik: 7, Številka: 78Journal Article
The SARS-CoV-2 Omicron variant and its sublineages show pronounced viral escape from neutralizing antibodies elicited by vaccination or prior SARS-CoV-2 variant infection owing to over 30-amino acid alterations within the spike (S) glycoprotein. Breakthrough infection of vaccinated individuals with Omicron sublineages BA.1 and BA.2 is associated with distinct patterns of cross-neutralizing activity against SARS-CoV-2 variants of concern (VOCs). In continuation of our previous work, we characterized the effect of Omicron BA.4/BA.5 S glycoprotein exposure on the neutralizing antibody response upon breakthrough infection in vaccinated individuals and upon variant-adapted booster vaccination in mice. We found that immune sera from triple mRNA-vaccinated individuals with subsequent breakthrough infection during the Omicron BA.4/BA.5 wave showed cross-neutralizing activity against previous Omicron variants BA.1, BA.2, BA.2.12.1, and BA.4/BA.5 itself. Administration of a prototypic BA.4/BA.5-adapted mRNA booster vaccine to mice after SARS-CoV-2 wild-type strain-based primary immunization is associated with broader cross-neutralizing activity than a BA.1-adapted booster. Whereas the Omicron BA.1-adapted mRNA vaccine in a bivalent format (wild-type + BA.1) broadens cross-neutralizing activity relative to the BA.1 monovalent booster, cross-neutralization of BA.2 and descendants is more effective in mice boosted with a bivalent wild-type + BA.4/BA.5 vaccine. In naïve mice, primary immunization with the bivalent wild-type + Omicron BA.4/BA.5 vaccine induces strong cross-neutralizing activity against Omicron VOCs and previous variants. These findings suggest that, when administered as boosters, mono- and bivalent Omicron BA.4/BA.5-adapted vaccines enhance neutralization breadth and that the bivalent version also has the potential to confer protection to individuals with no preexisting immunity against SARS-CoV-2.
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