TY - JOUR
T1 - Correlates of protection for booster doses of the SARS-CoV-2 vaccine BNT162b2
AU - Hertz, Tomer
AU - Levy, Shlomia
AU - Ostrovsky, Daniel
AU - Oppenheimer, Hanna
AU - Zismanov, Shosh
AU - Kuzmina, Alona
AU - Friedman, Lilach M.
AU - Trifkovic, Sanja
AU - Brice, David
AU - Chun-Yang, Lin
AU - Cohen-Lavi, Liel
AU - Shemer-Avni, Yonat
AU - Cohen-Lahav, Merav
AU - Amichay, Doron
AU - Keren-Naus, Ayelet
AU - Voloshin, Olga
AU - Weber, Gabriel
AU - Najjar-Debbiny, Ronza
AU - Chazan, Bibiana
AU - McGargill, Maureen A.
AU - Webby, Richard
AU - Chowers, Michal
AU - Novack, Lena
AU - Novack, Victor
AU - Taube, Ran
AU - Nesher, Lior
AU - Weinstein, Orly
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12/1
Y1 - 2023/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85165996001&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-39816-4
DO - 10.1038/s41467-023-39816-4
M3 - Article
C2 - 37516771
AN - SCOPUS:85165996001
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4575
ER -
