Correlates of protection for booster doses of the SARS-CoV-2 vaccine BNT162b2

Tomer Hertz (), Shlomia Levy, Daniel Ostrovsky, Hanna Oppenheimer, Shosh Zismanov, Alona Kuzmina, Lilach M. Friedman, Sanja Trifkovic, David Brice, Lin Chun-Yang, Liel Cohen-Lavi, Yonat Shemer-Avni, Merav Cohen-Lahav, Doron Amichay, Ayelet Keren-Naus, Olga Voloshin, Gabriel Weber, Ronza Najjar-Debbiny, Bibiana Chazan, Maureen A. McGargill, Richard Webby, Michal Chowers, Lena Novack, Victor Novack, Ran Taube (), Lior Nesher () and Orly Weinstein
Additional contact information
Tomer Hertz: Ben-Gurion University of the Negev
Shlomia Levy: Ben-Gurion University of the Negev
Daniel Ostrovsky: Soroka University Medical Center, and the faculty of Health Sciences, Ben-Gurion University of the Negev
Hanna Oppenheimer: Ben-Gurion University of the Negev
Shosh Zismanov: Ben-Gurion University of the Negev
Alona Kuzmina: Ben-Gurion University of the Negev
Lilach M. Friedman: Ben-Gurion University of the Negev
Sanja Trifkovic: St. Jude Children’s Research Hospital
David Brice: St. Jude Children’s Research Hospital
Lin Chun-Yang: St. Jude Children’s Research Hospital
Liel Cohen-Lavi: Ben-Gurion University of the Negev
Yonat Shemer-Avni: Ben-Gurion University of the Negev
Merav Cohen-Lahav: Soroka University Medical Center
Doron Amichay: Ben-Gurion University of the Negev
Ayelet Keren-Naus: Ben-Gurion University of the Negev
Olga Voloshin: Soroka University Medical Center
Gabriel Weber: Lady Davis Carmel Medical Center
Ronza Najjar-Debbiny: Lady Davis Carmel Medical Center
Bibiana Chazan: Technion-Israel Institute of Technology
Maureen A. McGargill: St. Jude Children’s Research Hospital
Richard Webby: St. Jude Children’s Research Hospital
Michal Chowers: Tel Aviv University
Lena Novack: Soroka University Medical Center, and the faculty of Health Sciences, Ben-Gurion University of the Negev
Victor Novack: Soroka University Medical Center, and the faculty of Health Sciences, Ben-Gurion University of the Negev
Ran Taube: Ben-Gurion University of the Negev
Lior Nesher: Soroka University Medical Center, and Faculty of Health Sciences, Ben-Gurion University
Orly Weinstein: Ben-Gurion University of the Negev

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Vaccination, especially with multiple doses, provides substantial population-level protection against COVID-19, but emerging variants of concern (VOC) and waning immunity represent significant risks at the individual level. Here we identify correlates of protection (COP) in a multicenter prospective study following 607 healthy individuals who received three doses of the Pfizer-BNT162b2 vaccine approximately six months prior to enrollment. We compared 242 individuals who received a fourth dose to 365 who did not. Within 90 days of enrollment, 239 individuals contracted COVID-19, 45% of the 3-dose group and 30% of the four-dose group. The fourth dose elicited a significant rise in antibody binding and neutralizing titers against multiple VOCs reducing the risk of symptomatic infection by 37% [95%CI, 15%-54%]. However, a group of individuals, characterized by low baseline titers of binding antibodies, remained susceptible to infection despite significantly increased neutralizing antibody titers upon boosting. A combination of reduced IgG levels to RBD mutants and reduced VOC-recognizing IgA antibodies represented the strongest COP in both the 3-dose group (HR = 6.34, p = 0.008) and four-dose group (HR = 8.14, p = 0.018). We validated our findings in an independent second cohort. In summary combination IgA and IgG baseline binding antibody levels may identify individuals most at risk from future infections.

Date: 2023
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DOI: 10.1038/s41467-023-39816-4

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