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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.

Figures

Figure 1.
Figure 1.
SARS-CoV-2 binding IgG and pseudovirus nAb activity in maternal and infant sera by study group and study visit. Pregnant participants received a 2-dose series of an mRNA vaccine (Primary series) or a booster (Booster), or were boosted postpartum (Booster postpartum) and based on the presence of N-protein IgG, were classified as N-protein IgG positive (N pos) or negative (N neg) as an indicator or past infection with SARS-CoV-2. Sera was derived from maternal blood collected at delivery or 2 months post-delivery, and from cord blood at delivery or from the infant at 2 months post-delivery. Sera were evaluated for binding IgG to full-length Spike (top panels) and RBD (middle panels), or pseudovirus nAb titers (IC50) (bottom panels). Binding IgG titers were bridged to international standards and reported as Binding Antibody Units (BAU/mL). Box plots represent median (horizontal line within the box) and interquartile range; the dashed line is the cutoff for positivity (17 BAU/mL) for Spike IgG. Geometric Mean Ratio (GMR) and P values are displayed for each comparison.
Figure 2.
Figure 2.
SARS-CoV-2 live virus nAb activity of maternal and infant sera by study group and study visit. Pregnant participants received a 2-dose series of an mRNA vaccine (top panels) or a booster (middle panels) or were boosted postpartum (bottom panels). Sera was derived from maternal blood collected at delivery or 2 months post-delivery, and from cord blood at delivery or from the infant at 2 months post-delivery. Sera were evaluated for neutralization of D614G, Omicron BA.1 or BA.5 variants. Each point represents the GMT ID50 from two duplicates per specimen (within the same assay run). A value equivalent to half the lower limit of detection (LLOD = 20; dashed line) was assigned to observations with no detectable response. Box plots represent median (horizontal line within the box) and interquartile range. GMT and fold reduction compared to D614G are displayed at the top of each panel.
Figure 3.
Figure 3.
SARS-CoV-2 Maternal and Infant Live Virus Neutralizing Antibodies Response Rate by Variant, Visit, and Study Group. The proportion of participants who had a detectable live virus neutralizing antibody response against D614G (left panel), BA.1.1.529 (Omicron) (middle panel) and BA.5 (Omicron) (right panel) is shown for maternal participants (top panel) and infant participants (bottom panel). Blue bars represent participants in the primary 2-dose series group, red bars represent participants in the booster dose during pregnancy group, and green bars represent participants in the booster dose postpartum group. Sera was derived from maternal blood collected at delivery or 2 months post-delivery, and from cord blood at delivery or from the infant at 2 months post-delivery. 95% confidence intervals shown for each response rate.
Figure 4.
Figure 4.
SARS-CoV-2 binding IgG and IgA in breast milk samples by study group at 2 months post-delivery. Pregnant participants received a 2-dose series of an mRNA vaccine (Primary series) or a booster (Booster) or were boosted postpartum (Booster postpartum) and based on the presence of N-protein IgG, were classified as N-protein IgG positive (N pos) or negative (N neg) as an indicator or past infection with SARS-CoV-2. Breast milk was obtained at 2 months post-delivery and evaluated for binding IgG (left panels) and IgA (right panels) to full-length Spike (top panels) and RBD (bottom panels). Binding IgG and IgA titers were bridged to international standards and reported as Binding Antibody Units (BAU/mL). Box plots represent median (horizontal line within the box) and interquartile range; the dashed lines are the cutoffs for positivity (0.03 BAU/mL for Spike IgG; 3.7 BAU/mL for Spike IgA).
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