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

Paul R. Wratil, Marcel Stern, Alina Priller, Annika Willmann, Giovanni Almanzar, Emanuel Vogel, Martin Feuerherd, Cho Chin Cheng, Sarah Yazici, Catharina Christa, Samuel Jeske, Gaia Lupoli, Tim Vogt, Manuel Albanese, Ernesto Mejías-Pérez, Stefan Bauernfried, Natalia Graf, Hrvoje Mijocevic, Martin Vu, Kathrin TinnefeldJochen Wettengel, Dieter Hoffmann, Maximilian Muenchhoff, Christopher Daechert, Helga Mairhofer, Stefan Krebs, Volker Fingerle, Alexander Graf, Philipp Steininger, Helmut Blum, Veit Hornung, Bernhard Liebl, Klaus Überla, Martina Prelog, Percy Knolle, Oliver T. Keppler, Ulrike Protzer

Research output: Contribution to journalArticlepeer-review

170 Scopus citations

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.

Original languageEnglish
Pages (from-to)496-503
Number of pages8
JournalNature Medicine
Volume28
Issue number3
DOIs
StatePublished - Mar 2022
Externally publishedYes

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