Assessment of Adverse Reactions, Antibody Patterns, and 12-month Outcomes in the Mother-Infant Dyad After COVID-19 mRNA Vaccination in Pregnancy

Abstract

ImportanceLongitudinal data on COVID-19 messenger RNA (mRNA) vaccine reactogenicity and immunogenicity in pregnancy and for the mother-infant dyad are needed.ObjectiveTo examine COVID-19 mRNA vaccine reactogenicity and immunogenicity in pregnancy and observe longitudinal maternal and infant outcomes.Design, Setting, and ParticipantsThis 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.ExposureCOVID-19 mRNA vaccination at any time during pregnancy.Main Outcomes and MeasuresThe 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.ResultsOf 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.Conclusions and RelevanceThe 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.

Placental transfer dynamics and durability of maternal COVID-19 vaccine-induced antibodies in infants

“…Previous studies have demonstrated that timing of initiation of COVID-19 vaccination in pregnancy influenced the levels of maternal vaccine-induced antibodies at delivery and transplacental transfer to the umbilical cord 14,16,24,33,34 . Knowledge is lacking, however, regarding how the timing of not only the first, but also the second dose of the mRNA vaccine in pregnancy, impacts maternal antibody levels and persistence of antibody in infants.…”

“…Maternal vaccination against COVID-19 has been shown to effectively reduce COVID-19 related hospitalization rates in infants younger than 6 months 9,10 , through the transplacental transfer of maternal COVID-19 vaccine induced antibodies 16,17 . Here, using systems serology, we profiled maternal antibodies in 100 infants up to 12 months of age in unprecedented detail.…”

“…These studies did not examine antibody levels in infants, nor did they examine the impact of vaccination timing within the second half of pregnancy on infant protection. While there are limited data available on antibody levels in infants after maternal COVID-19 vaccination 16,17 , these studies have not examined how timing of vaccination across a range of trimesters or within trimester impacts infant antibody levels. There are also no data on relative persistence of different IgG subclasses, nor on FcR binding, or activity against VOCs in infants within the first year of life.…”

“…Recent studies examining COVID-19 vaccination during pregnancy have demonstrated the transplacental antibody transfer of anti-Spike immunoglobin (Ig) G antibodies 12–16 . While there are limited data on the persistence of maternal anti-Spike IgG antibodies in infants 16,17 , no study has performed comprehensive profiling of maternal COVID-19 vaccine-induced antibodies that persist in infants through 12 months of age, including all IgG subclasses, Fc receptor (FcR) binding profiles, and against both SARS-CoV-2 wild-type and variants of concern (VOCs) including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), P.1 (Gamma), and B.1.1.529 (Omicron) variants. FcR binding is a critical consideration, as the Fc region of the antibodies plays an important role in protection against infection and the resolution of SARS-CoV-2 infection 18,19 by inducing the antiviral activity of the innate immune system 20,21 .…”

Placental transfer dynamics and durability of maternal COVID-19 vaccine-induced antibodies in infants

“…Recent studies examining COVID-19 vaccination during pregnancy have demonstrated the transplacental antibody transfer of anti-spike immunoglobin (Ig) G antibodies. 12 , 13 , 14 , 15 , 16 While there are limited data on the persistence of maternal anti-spike IgG antibodies in infants, 16 , 17 no study has performed comprehensive profiling of maternal COVID-19 vaccine-induced antibodies that persist in infants through 12 months of age, including all IgG subclasses, Fc-receptor (FcR) binding profiles, and against both SARS-CoV-2 wild-type and variants of concern (VOCs) including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), P.1 (Gamma), and B.1.1.529 (Omicron) variants. FcR binding is a critical consideration, as the Fc region of the antibodies plays an important role in protection against infection and the resolution of SARS-CoV-2 infection 18 , 19 by inducing the antiviral activity of the innate immune system.…”