COVID-19 booster dose antibody response in pregnant, lactating, and nonpregnant women

BACKGROUND While emerging data during the SARS-CoV-2 pandemic have demonstrated robust mRNA vaccine-induced immunogenicity across populations, including pregnant and lactating individuals, the rapid waning of vaccine-induced immunity and the emergence of variants of concern motivated the use of mRNA vaccine booster doses. Whether all populations, including pregnant and lactating individuals, will mount a comparable response to a booster dose is not known. OBJECTIVE We sought to profile the humoral immune response to a COVID-19 mRNA booster dose in a cohort of pregnant, lactating, and age-matched nonpregnant women. STUDY DESIGN We characterized the antibody response against ancestral Spike and Omicron in a cohort of 31 pregnant, 12 lactating and 20 nonpregnant age-matched controls who received a BNT162b2 or mRNA-1273 booster dose after primary COVID-19 vaccination. We also examined the vaccine-induced antibody profiles of 15 maternal:cord dyads at delivery. RESULTS Receipt of a booster dose during pregnancy resulted in increased IgG1 against Omicron Spike (post-primary vaccination vs post-booster, p = 0.03). Pregnant and lactating individuals exhibited equivalent Spike-specific total IgG1, IgM and IgA levels and neutralizing titers against Omicron compared to nonpregnant women. Subtle differences in Fc-receptor binding and antibody subclass profiles were observed in the immune response to a booster dose in pregnant compared to nonpregnant individuals. Analysis of maternal and cord antibody profiles at delivery demonstrated equivalent total Spike-specific IgG1 in maternal and cord blood, yet higher Spike-specific FcγR3a-binding antibodies in the cord relative to maternal blood (p = 0.002), consistent with preferential transfer of highly functional IgG. Spike-specific IgG1 levels in the cord were positively correlated with time elapsed since receipt of the booster dose (Spearman R 0.574, p = 0.035). CONCLUSIONS These data suggest that receipt of a booster dose during pregnancy induces a robust Spike-specific humoral immune response, including against Omicron. If boosting occurs in the third trimester, higher Spike-specific cord IgG1 levels are achieved with greater time elapsed between receipt of the booster and delivery. Receipt of a booster dose has the potential to augment maternal and neonatal immunity. ### Competing Interest Statement K.J.G. has consulted for Illumina, BillionToOne, Aetion, and Roche outside the scope of the submitted work. G.A. is the founder of Seromyx Inc. A.G.E. reported serving as a medical advisor for Mirvie. A.F. reported serving as a cofounder of and owning stock in Alba Therapeutics and serving on scientific advisory boards for NextCure and Viome outside the submitted work. All other authors report no competing interests. ### Funding Statement This study was funded by: NICHD: 1R01HD100022-01 and 3R01HD100022-02S2 to A.G.E. and 1K12HD103096 to L.L.S., March of Dimes Grant 6-FY20-223 to A.G.E., NIH/NHLBI: K08HL1469630-03 and 3K08HL146963-02S1 to K.J.G., Ragon Institute of MGH, MIT, and Harvard and the MGH ECOR Scholars award to G.A., Nancy Zimmerman, SAMANA Kay MGH Research Scholars award to G.A., an anonymous donor, the Massachusetts Consortium on Pathogen Readiness (MassCPR), the NIH: 3R37AI080289-11S1, R01AI146785, U19AI42790-01, U19AI135995-02, 1U01CA260476-01, and CIVIC5N93019C00052 to G.A., the Gates Foundation Global Health Vaccine Accelerator Platform funding: OPP1146996 and INV-001650 to G.A., and the Musk Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Institutional Review Board of Massachusetts General Brigham gave ethical approval for this work (Protocol#2020P003538, Date of Approval 12/14/2020). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data in the present study are available upon reasonable request to the authors.