Completion of a COVID-19 vaccination series during pregnancy effectively reduces COVID-19 hospitalization among infants less than 6 months of age. Elucidating the dynamics of transplacental transfer of maternal vaccine-induced antibodies, and their persistence in infants at 2, 6, 9 and 12 months, has implications for new vaccine development and timing of vaccine administration in pregnancy to optimize protection of the mother-infant dyad. We evaluated anti-COVID antibody IgG subclass, Fc-receptor binding profile, and activity against wild-type Spike and RBD, and five variants of concern (VOCs) in 153 serum samples from 100 unique infants. Maternal IgG1 and IgG3 responses persisted in 2- and 6-month infants to a greater extent than the other IgG subclasses, with highest persistence of antibodies that bind placental neonatal Fc-receptor as well as FcgR3A. Timing of maternal vaccination and fetal sex were drivers of antibody persistence in infants. Lowest persistence at 2 and 6 months was observed against the Omicron RBD-specific region. Maternal vaccine timing, placental Fc-receptor binding capabilities, antibody subclass, fetal sex, and VOC all impact the persistence of maternal vaccine-induced antibodies in infants up to 12 months.

This work was supported in part by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp (MISP 61299 to A.G.E.). The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme Corp. K.J.G. has consulted for Illumina, BillionToOne, and Aetion outside the scope of the submitted work. A.G.E. and M.A.E. serve as medical advisors for Mirvie. M.A.E has equity in Mirvie outside the submitted work. B.D.J.'s immediate family member, Galit Alter, is co-founder of Seromyx Systems, Inc., and has a patent on Systems Serology Platform pending.

This study was funded by: Merck Sharp & Dohme Corp Investigator-Initiated Studies grant (MISP 61299, to A.G.E.); NIH/NIAID 1U19AI167899-01 to D.A.L., A.G.E., M.A.E., B.D.J.; NIH/NHLBI 5K08HL143183 to L.M.Y

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