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.