Correlates of protection for booster doses of the SARS-CoV-2 vaccine BNT162b2
Tomer Hertz, Shlomia Levy, Daniel Ostrovsky, H. R. Oppenheimer, Shosh Zismanov, Alona Kuzmina, Lilach M. Friedman, Sanja Trifkovic, David C. Brice, Lin Chun-Yang, Liel Cohen-Lavi, Yonat Shemer‐Avni, M. Cohen, Doron Amichay, Ayelet Keren‐Naus, Olga Voloshin, Regina Weber, Ronza Najjar‐Debbiny, Bibiana Chazan, Maureen A. McGargill, Richard J. Webby, Michal Chowers, Lena Novack, Victor Novack, Ran Taube, Lior Nesher, Orly Weinstein
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.