Three exposures to the spike protein of SARS-CoV-2 by either infection or vaccination elicit superior neutralizing immunity to all variants of concern

Wratil, Paul R.; Stern, Marcel; Priller, Alina; Willmann, Annika; Almanzar, Giovanni; Vogel, Emanuel; Feuerherd, Martin; Cheng, Cho-Chin; Yazici, Sarah; Christa, Catharina; Jeske, Samuel; Lupoli, Gaia; Vogt, Tim; Albanese, Manuel; Mejias-Perez, Ernesto; Bauernfried, Stefan; Graf, Natalia; Mijocevic, Hrvoje; Vu, Martin; Tinnefeld, Kathrin; Wettengel, Jochen; Hoffmann, Dieter; Muenchhoff, Maximilian; Daechert, Christopher; Mairhofer, Helga; Krebs, Stefan; Fingerle, Volker; Graf, Alexander; Steininger, Philipp; Blum, Helmut; Hornung, Veit; Liebl, Bernhard; Ueberla, Klaus; Prelog, Martina; Knolle, Percy; Keppler, Oliver T. und Protzer, Ulrike (2022): Three exposures to the spike protein of SARS-CoV-2 by either infection or vaccination elicit superior neutralizing immunity to all variants of concern. In: Nature Medicine, Vol. 28, No. 3: pp. 496-503

Abstract

Infection-neutralizing antibody responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 vaccination are an essential component of antiviral immunity. Antibody-mediated protection is challenged by the emergence of SARS-CoV-2 variants of concern (VoCs) with immune escape properties, such as omicron (B.1.1.529), which is rapidly spreading worldwide. Here we report neutralizing antibody dynamics in a longitudinal cohort of coronavirus disease 2019 convalescent and infection-naive individuals vaccinated with mRNA BNT162b2 by quantifying SARS-CoV-2 spike protein antibodies and determining their avidity and neutralization capacity in serum. Using live-virus neutralization assays, we show that a superior infection-neutralizing capacity against all VoCs, including omicron, developed after either two vaccinations in convalescents or a third vaccination or breakthrough infection of twice-vaccinated, naive individuals. These three consecutive spike antigen exposures resulted in an increasing neutralization capacity per anti-spike antibody unit and were paralleled by stepwise increases in antibody avidity. We conclude that an infection-plus-vaccination-induced hybrid immunity or a triple immunization can induce high-quality antibodies with superior neutralization capacity against VoCs, including omicron.

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy > Department of Biochemistry
• Subjects: 500 Science > 540 Chemistry
• ISSN: 1078-8956
• Language: English