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. 2024 Nov 1;43(11):1065-1073.
doi: 10.1097/INF.0000000000004510. Epub 2024 Aug 13.

Enhanced D614G and Omicron Variants Antibody Persistence in Infants at 2 Months of Age Following Maternal mRNA Booster Vaccination During Pregnancy or Postpartum

Flor M Munoz  1 , Richard Beigi  2 , Christine M Posavad  3 , Clifton Kelly  4 , Martina L Badell  5 , Katherine Bunge  2 , Mark J Mulligan  6 , Lalitha Parameswaran  6 , Barbra A Richardson  7 , Courtney Olsen-Chen  8 , Richard M Novak  9 , Rebecca C Brady  10 , Emily DeFranco  10 , Jeffrey S Gerber  11 , Mallory Shriver  12 , Mehul S Suthar  13 , Rhea Coler  14 , Bryan J Berube  14 , So Hee Kim  4 , Jeanna M Piper  15 , Joy Miedema  16 , Marcela Pasetti  12 , Kathleen M Neuzil  12 , Cristina V Cardemil  15 ; DMID Study Group
Affiliations

Enhanced D614G and Omicron Variants Antibody Persistence in Infants at 2 Months of Age Following Maternal mRNA Booster Vaccination During Pregnancy or Postpartum

Flor M Munoz et al. Pediatr Infect Dis J. .

Abstract

Background: Following maternal COVID-19 vaccination, the persistence of antibodies in sera and breast milk for mothers and infants is not well characterized. We sought to describe the persistence of antibodies through 2 months after delivery in maternal and infant serum and breast milk following maternal COVID-19 mRNA vaccination and to examine differences by receipt of booster dose during pregnancy or postpartum.

Methods: This is a prospective cohort study with enrollment from July 2021 to January 2022 at 9 US academic sites. Pregnant or postpartum participants and their infants were enrolled after COVID-19 mRNA monovalent vaccination during pregnancy (primary 2-dose series) with booster (third dose) vaccination during pregnancy or within 2 months post-partum. SARS-CoV-2-binding and functional antibody responses at delivery and 2 months after delivery in mothers and infants were measured by spike and receptor-binding domain immunoglobulin (Ig) G, pseudovirus and live neutralizing antibody (nAb) titers to ancestral and Omicron BA.1 and BA.5 strains. Breast milk spike and receptor-binding domain IgG and IgA titers were also measured.

Results: A total of 237 maternal/infant dyads were included (110 primary series during pregnancy, 99 pregnancy booster and 28 postpartum booster). A pregnancy booster resulted in 2.2-4.7-fold higher IgG and nAb at delivery and 2 months for both mothers and infants compared to the primary series alone (P < 0.001 for all comparisons). While infant IgG and nAb titers decreased by 2 months of age, the proportion of infants with detectable nAb at 2 months was greater in infants of mothers boosted during pregnancy compared with primary series for all variants (D614G: 99% vs. 56%; BA.1: 56% vs. 4% and BA.5: 57% vs. 9%; P < 0.001 for all comparisons). Breast milk spike IgA and IgG were present in 64%-100% and 100% of participants, respectively, and those boosted during pregnancy or postpartum had 3.1-4.6-fold higher levels of breast milk antibodies at 2 months compared to primary series during pregnancy (P < 0.001).

Conclusions: mRNA COVID-19 monovalent booster vaccination during pregnancy results in significantly higher maternal and infant serum-binding IgG and nAb titers compared to a primary 2-dose series, including against Omicron variants, through 2 months of age. Breast milk antibodies following maternal vaccination during pregnancy or postpartum may provide additional protection during early infancy.

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Conflict of interest statement

F.M.M. is an investigator of pediatric studies of COVID-19 vaccines for Pfizer and for a pediatric Remdesivir study conducted by Gilead Sciences, Inc; serves as an investigator on projects supported by a National Institutes of Health (NIH) contract for a Vaccine Treatment and Evaluation Unit (VTEU), serves as a member of the Data Safety Monitoring Board (DSMB) for clinical trials conducted by Pfizer, Moderna, Meissa Vaccines, Virometix and the NIH; is a member of the American Academy of Pediatrics Section of Infectious Diseases and the Immunization Expert Group of the American College of Obstetrics and Gynecology; and Chair of the Coalition for Epidemic Preparedness and Innovation-Safety Platform for Emergency Vaccines (CEPI-SPEAC) Maternal Immunization Working Group. K.M.N. is a member of the World Health Organization Strategic Advisory Group of Experts on Immunization, serves as co-investigator on an NIH contract for a VTEU and the Co-Chair of the NIH COVID Prevention Network and served as an investigator for Phase I/II Pfizer COVID-19 vaccine grant, with a grant to the institution, but no salary support. K.M.N. receives grants from Pfizer to conduct clinical trials of COVID vaccines through the Center for Vaccine Development and Global Health at the University of Maryland, Baltimore. K.M.N. receives grants from NIH to participate in the overall organization of COVID-19 vaccine trials and for participation in vaccine trials. M.J.M. conducts laboratory research and clinical trials with contract funding for vaccines or monoclonal antibodies versus SARS-CoV-2 with Lilly, Pfizer and Sanofi and receives personal fees for the Scientific Advisory Board service from Merck, Meissa Vaccines, Inc, and Pfizer. M.S.S. served as an advisor for Moderna (ended December 2021) and is currently serving as an advisor for Ocugen, Inc. B.A.R. currently holds a position on a DSMB for clinical trials at Gilead Sciences, Inc. R.C.B. at Cincinnati Children’s Hospital receives research grant support for clinical trials from PATH, Astra Zeneca and Pfizer in which she serves as a co-investigator. B.B. owns shares in HDT Bio Corp. J.S.G. receives research funds from NIH for the Moderna KidCOVE study. R.M.N. is a paid advisor to Gilead and an investigator on NIH-funded trials of Moderna, Pfizer and Janssen vaccines. All authors have completed relevant conflicts of interest in the Disclosure of Potential Conflicts of Interest Section of the Authorship Form.

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