Protection After First Dose of COVID-19 mRNA Vaccines Slower to Develop in Pregnant Women

Initial trials of COVID-19 vaccines excluded pregnant and lactating women because of safety concerns. Around the same time, it became clear pregnancy is a risk factor for severe COVID-19. This makes it particularly important to understand how pregnancy and lactation influence immunological responses to COVID-19 vaccination.

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Andrea G. Edlow, MD, MSc, an investigator in the Vincent Center for Reproductive Biology and in the Department of Obstetrics and Gynecology at Massachusetts General Hospital, together with Galit Alter, PhD, principal investigator at the Ragon Institute of Massachusetts General Hospital, MIT and Harvard, and Samana Cay MGH Research Scholar, and Caroline Atyeo, PhD candidate, and other colleagues, have detected differences among pregnant, lactating and nonpregnant women in vaccine-induced antibody profiles that highlight the critical importance of administering second vaccine doses on time. Their findings appear in Science Translational Medicine.

Study Methods

The researchers used systems serology to comprehensively profile the humoral immune response in 84 pregnant women, 31 lactating women and 16 nonpregnant age-matched female controls who received either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine.

Women could be vaccinated during any trimester of pregnancy; the mean gestational age at the time of first vaccination was 23 weeks. Blood/breastmilk samples were obtained three to four weeks after the first dose (i.e., at the time of the second dose) and two to 5.5 weeks after the second dose.

After the First Dose

• Pregnant and lactating women had similar antibody responses
• Antibody titers and Fc–receptor (FcR) binding across all FcRs were lower in pregnant/lactating women than nonpregnant women

FcR binding is not only critical to activating immune cells but also plays a key role in the transfer of maternal antibodies to the fetus through the placenta.

After the Second Dose

• The vaccine response differed between pregnant and lactating women, with lactating women overall more similar to nonpregnant women
• FcR binding and antibody effector functions normalized in both pregnant and lactating women after the second dose
• Functional antibodies for natural killer cell activity and neutrophil phagocytosis were higher in lactating women than in either pregnant or nonpregnant women
• Both the mRNA-1273 and BNT162b2 vaccines induced highly effective antibody responses
• Optimal vaccine-induced antibody transfer to breastmilk was highly dependent on the second dose

Take-home Messages

Pregnancy appears to alter the kinetics of antibody production after the COVID-19 mRNA vaccines. Thus, the window of vulnerability after initial vaccination may be extended in pregnant and lactating women.

There is a critical need to administer two COVID-19 mRNA vaccine doses at the recommended interval in this population to achieve the fully functional antibodies needed to protect the pregnant woman and her infant.

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