Pregnant and lactating women were excluded from initial COVID-19 vaccine trials; thus, data to guide vaccine decision-making are lacking.
To evaluate the immunogenicity and reactogenicity of COVID-19 mRNA vaccination in pregnant and lactating women compared to: (1) non-pregnant controls and (2) natural COVID-19 infection in pregnancy.
131 reproductive-age vaccine recipients (84 pregnant, 31 lactating, and 16 non-pregnant) were enrolled in a prospective cohort study at two academic medical centers. Titers of SARS-CoV-2 Spike and RBD IgG, IgA and IgM were quantified in participant sera (N=131) and breastmilk (N=31) at baseline, second vaccine dose, 2-6 weeks post second vaccine, and at delivery by Luminex. Umbilical cord sera (N=10) titers were assessed at delivery. Titers were compared to those of pregnant women 4-12 weeks from natural infection (N=37) by ELISA. A pseudovirus neutralization assay was used to quantify neutralizing antibody titers for the subset of women who delivered during the study period. Post-vaccination symptoms were assessed via questionnaire. Kruskal-Wallis tests and a mixed effects model, with correction for multiple comparisons, were used to assess differences between groups.
Vaccine-induced antibody titers were equivalent in pregnant and lactating compared to non-pregnant women (median [IQR] 5.59 [4.68-5.89] pregnant, 5.74 [5.06-6.22] lactating, 5.62 [4.77-5.98] non-pregnant, p = 0.24). All titers were significantly higher than those induced by SARS-CoV-2 infection during pregnancy (p < 0.0001). Vaccine-generated antibodies were present in all umbilical cord blood and breastmilk samples. Neutralizing antibody titers were lower in umbilical cord compared to maternal sera, although this finding did not achieve statistical significance (median [IQR] 104.7 [61.2-188.2] maternal sera, 52.3 [11.7-69.6] cord sera, p=0.05). The second vaccine dose (boost dose) increased SARS-CoV-2-specific IgG, but not IgA, in maternal blood and breastmilk. No differences were noted in reactogenicity across the groups.
COVID-19 mRNA vaccines generated robust humoral immunity in pregnant and lactating women, with immunogenicity and reactogenicity similar to that observed in non-pregnant women. Vaccine-induced immune responses were significantly greater than the response to natural infection. Immune transfer to neonates occurred via placenta and breastmilk.
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In Press Journal Pre-Proof
KJG has consulted for Illumina, BillionToOne, and Aetion outsite the submitted work. AF 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. GA reported serving as a founder of Systems Seromyx. MAE reported serving as medical advisor for Mirvie. All other authors report no conflicts of interest.
SOURCES OF FUNDING:
This work was supported by the National Institutes of Health, including NICHD (grants R01HD100022 and 3R01HD100022-02S20-to AGE), NHLBI (grants K08HL1469630-02 and 3K08HL146963-02S1-to KJG). Additional support was provided by NIAID (3R37AI080289-11S1, R01AI146785, U19AI42790-01, U19AI135995-02, U19AI42790-01, 1U01CA260476 – 01- to GA; R01A1145840-supplement to MAE), the Gates Foundation, the Massachusetts Consortium on Pathogen Readiness (MassCPR), the Musk Foundation, the Ragon Institute of MGH and MIT and the Massachusetts General Hospital and Brigham and Women’s Hospital Departments of Obstetrics and Gynecology.
CONDENSATION: COVID-19 vaccination confers a robust humoral response in pregnant and lactating women and immune transfer to neonates via placenta and breastmilk.
AJOG at a GLANCE:
A. Why was this study conducted? Because pregnant and lactating women were excluded from initial COVID-19 vaccine trials, data are lacking regarding vaccine efficacy and infant humoral protection in this population.
B. What are the key findings? Pregnant and lactating women elicited comparable vaccine-induced humoral immune responses to non-pregnant controls, and generated higher antibody titers than those observed following SARS-CoV-2 infection in pregnancy. Vaccine-generated antibodies were present in umbilical cord blood and breastmilk after maternal vaccination.
C. What does this study add to what is already known? This study provides the first data from a large cohort on maternal antibody generation in response to COVID-19 vaccination, compares vaccine-generated immunity to that from natural infection in pregnancy, and suggests vaccination of pregnant and lactating women can confer robust maternal and neonatal immunity.
© 2021 The Author(s). Published by Elsevier Inc.