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

• Published in: Nature medicine Vol. 28; no. 3; pp. 496 - 503
• Main Authors: 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, Mejías-Pérez, 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, Überla, Klaus, Prelog, Martina, Knolle, Percy, Keppler, Oliver T, Protzer, Ulrike
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.03.2022
• Subjects: Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Antigens; Avidity; BNT162 Vaccine - immunology; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - prevention & control; Disease transmission; Exposure; Humans; Immunity; Immunization; Infections; mRNA; Neutralization; Neutralizing; Proteins; Respiratory diseases; SARS-CoV-2 - immunology; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - immunology; Spike protein; Vaccination; Vaccines; Viral diseases; Viruses
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/s41591-022-01715-4

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.