Longitudinal data on COVID-19 messenger RNA (mRNA) vaccine reactogenicity and immunogenicity in pregnancy and for the mother-infant dyad are needed.
To examine COVID-19 mRNA vaccine reactogenicity ...and immunogenicity in pregnancy and observe longitudinal maternal and infant outcomes.
This prospective cohort study of pregnant individuals enrolled in the COVID-19 Vaccination in Pregnancy and Lactation study from December 1, 2020, through December 31, 2021, with follow-up through March 31, 2022, was conducted at a large academic medical center in an urban metropolitan area in California. Pregnant individuals receiving COVID-19 mRNA vaccines (mRNA-1273 Moderna and BNT162b2 Pfizer-BioNTech) were eligible. Of 81 participants enrolled, 5 were excluded after enrollment: 1 terminated pregnancy, 1 received the third vaccine dose prior to delivery, and 3 delivered prior to completing the initial vaccine series.
COVID-19 mRNA vaccination at any time during pregnancy.
The primary outcomes were vaccine response as measured by blood Immunoglobulin G (IgG) titers after each vaccine dose and self-reported postvaccination symptoms. Patients' IgG titers were measured in cord blood and in infant blood at intervals up to 1 year of life; IgG and IgA titers were measured in maternal milk. Clinical outcomes were collected from medical records.
Of 76 pregnant individuals included in final analyses (median IQR maternal age, 35 29-41 years; 51 67.1% White; 28 36.8% primigravid; 37 48.7% nulliparous), 42 (55.3%) received BNT162b2 and 34 (44.7%) received mRNA-1237. There were no significant differences in maternal characteristics between the 2 vaccine groups. Systemic symptoms were more common after receipt of the second vaccine dose than after the first dose (42 of 59 71.2% vs 26 of 59 44.1%; P = .007) and after mRNA-1237 than after BNT162b2 (25 of 27 92.6% vs 17 of 32 53.1%; P = .001). Systemic symptoms were associated with 65.6% higher median IgG titers than no symptoms after the second vaccine dose (median IQR, 2596 1840-4455 vs 1568 1114-4518 RFU; P = .007); mean cord titers in individuals with local or systemic symptoms were 6.3-fold higher than in individuals without symptoms. Vaccination in all trimesters elicited a robust maternal IgG response. The IgG transfer ratio was highest among individuals vaccinated in the second trimester. Anti-SARS-CoV-2 IgG was detectable in cord blood regardless of vaccination trimester. In milk, IgG and IgA titers remained above the positive cutoff for at least 5-6 months after birth, and infants of mothers vaccinated in the second and third trimesters had positive IgG titers for at least 5 to 6 months of life. There were no vaccine-attributable adverse perinatal outcomes.
The findings of this cohort study suggest that mRNA COVID-19 vaccination in pregnancy provokes a robust IgG response for the mother-infant dyad for approximately 6 months after birth. Postvaccination symptoms may indicate a more robust immune response, without adverse maternal, fetal, or neonatal outcomes.
Pregnancy confers unique immune responses to infection and vaccination across gestation. To date, there are limited data comparing vaccine- and infection-induced neutralizing Abs (nAbs) against ...COVID-19 variants in mothers during pregnancy. We analyzed paired maternal and cord plasma samples from 60 pregnant individuals. Thirty women vaccinated with mRNA vaccines (from December 2020 through August 2021) were matched with 30 naturally infected women (from March 2020 through January 2021) by gestational age of exposure. Neutralization activity against the 5 SARS-CoV-2 spike sequences was measured by a SARS-CoV-2-pseudotyped spike virion assay. Effective nAbs against SARS-CoV-2 were present in maternal and cord plasma after both infection and vaccination. Compared with WT spike protein, these nAbs were less effective against the Delta and Mu spike variants. Vaccination during the third trimester induced higher cord-nAb levels at delivery than did infection during the third trimester. In contrast, vaccine-induced nAb levels were lower at the time of delivery compared with infection during the first trimester. The transfer ratio (cord nAb level divided by maternal nAb level) was greatest in mothers vaccinated in the second trimester. SARS-CoV-2 vaccination or infection in pregnancy elicits effective nAbs with differing neutralization kinetics that are influenced by gestational time of exposure.
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