☆ 4.8 Article

COVID-19 mRNA vaccines drive differential antibody Fc-functional profiles in pregnant, lactating, and nonpregnant women

SCIENCE TRANSLATIONAL MEDICINE (2021)

Journal

SCIENCE TRANSLATIONAL MEDICINE

Volume 13, Issue 617, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE

DOI: 10.1126/scitranslmed.abi8631

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Funding

NIH-NHLBI [K08HL1469630-02, 3K08HL146963-02S1]
NICHD [1R01HD100022-01, 3R01HD100022-02S2]
March of Dimes [6-FY20-223]
Ragon Institute of MGH, MIT, and Harvard
MGH ECOR Scholars award
SAMANA Kay MGH Research Scholars award
Massachusetts Consortium on Pathogen Readiness (MassCPR)
NIH [3R37AI080289-11S1, R01AI146785, U19AI42790-01, U19AI135995-02, 1U01CA260476-01, CIVIC5N93019C00052]
Gates Foundation Global Health Vaccine Accelerator Platform funding [OPP1146996, INV-001650]
Musk Foundation
Bill and Melinda Gates Foundation [INV-001650] Funding Source: Bill and Melinda Gates Foundation

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Abstract

During pregnancy, significant immunological changes occur to make the mother immunologically tolerant to the fetus and continue to protect the dyad against pathogens during and after birth. Pregnant women may be less responsive to vaccination or exhibit altered immune responses to vaccination, highlighting the importance of following prime-boost timelines to ensure full immunity is attained in this vulnerable population.

Substantial immunological changes occur throughout pregnancy to render the mother immunologically tolerant to the fetus and allow fetal growth. However, additional local and systemic immunological adaptations also occur, allowing the maternal immune system to continue to protect the dyad against pathogens both during pregnancy and after birth through lactation. This fine balance of tolerance and immunity, along with physiological and hormonal changes, contributes to increased susceptibility to particular infections in pregnancy, including more severe coronavirus disease 2019 (COVID-19). Whether these changes also make pregnant women less responsive to vaccination or induce altered immune responses to vaccination remains incompletely understood. To define potential changes in vaccine response during pregnancy and lactation, we undertook deep sequencing of the humoral vaccine response in a group of pregnant and lactating women and nonpregnant age-matched controls. Vaccine-specific titers were comparable between pregnant women, lactating women, and nonpregnant controls. However, Fc receptor (FcR) binding and antibody effector functions were induced with delayed kinetics in both pregnant and lactating women compared with nonpregnant women after the first vaccine dose, which normalized after the second dose. Vaccine boosting resulted in high FcR-binding titers in breastmilk. These data suggest that pregnancy promotes resistance to generating proinflammatory antibodies and indicates that there is a critical need to follow prime-boost timelines in this vulnerable population to ensure full immunity is attained.

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Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women

Ai-ris Y. Collier, Katherine McMahan, Jingyou Yu, Lisa H. Tostanoski, Ricardo Aguayo, Jessica Ansel, Abishek Chandrashekar, Shivani Patel, Esther Apraku Bondzie, Daniel Sellers, Julia Barrett, Owen Sanborn, Huahua Wan, Aiquan Chang, Tochi Anioke, Joseph Nkolola, Connor Bradshaw, Catherine Jacob-Dolan, Jared Feldman, Makda Gebre, Erica N. Borducchi, Jinyan Liu, Aaron G. Schmidt, Todd Suscovich, Caitlyn Linde, Galit Alter, Michele R. Hacker, Dan H. Barouch

Summary: This study assessed the immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women, as well as the responses against emerging SARS-CoV-2 variants. The results showed that pregnant, lactating, and nonpregnant women developed antibody and T-cell responses following vaccination, with antibodies transferred to infant cord blood and breast milk. While antibody titers against the B.1.1.7 and B.1.351 variants were reduced, T-cell responses remained against the viral variants.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2021)