Which COVID-19 vaccine type and timing are best during pregnancy?

BOSTON – Although pregnant individuals and newborns may face elevated risks of developing more severe cases of COVID-19 following SARS-CoV-2 infection, data indicate that COVID-19 vaccination during pregnancy can help to protect both the mother and child. New research collaboratively led by investigators at Massachusetts General Hospital (MGH) and Brigham and Women’s Hospital (BWH) and published in Nature Communications examined how different COVID-19 vaccines and the timing of vaccination during pregnancy impact the extent of this protection.

“Our goal was to compare maternal antibody responses and transplacental transfer of antibody to the neonate with vaccination across all three trimesters of pregnancy, and across different vaccine platforms (Moderna, Pfizer, and Johnson & Johnson). We hope to use this information to better counsel patients wondering about vaccination in the first versus the second or third trimester,” says co–senior author Andrea Edlow, MD, MSc, a maternal-fetal medicine specialist at MGH and an assistant professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School.

For the study, Edlow and her colleagues characterized antibody responses after Janssen’s adenovirus-based Ad26.COV2.S, Moderna’s mRNA-based mRNA-1273, and Pfizer-BioNTech’s mRNA-based BNT162b2 vaccines in 158 pregnant individuals. The team also evaluated the transfer of protective SARS-CoV-2 antibodies via the placenta from mother to fetus by analyzing maternal and umbilical cord blood in 175 maternal-neonatal pairs.

The research revealed induction of lower-functioning SARS-CoV-2-specific antibodies after Ad26.COV2.S compared with mRNA vaccination, as well as subtle advantages in antibody levels and function with mRNA-1273 versus BN162b2. mRNA vaccine-induced antibodies had higher levels and functions against SARS-CoV-2 variants of concern, such as Alpha, Beta, Delta, and Gamma. Vaccine-induced antibodies also demonstrated neutralizing activity against Omicron. First and third trimester vaccination led to enhanced maternal immune responses relative to second trimester vaccination. The transfer of SARS-CoV-2-specific antibodies to the fetus through the placenta was most efficient following first and second trimester vaccination.

“These data support the initial vaccine series early in pregnancy if it has not yet been administered, with possible boosting later in pregnancy if eligible, to optimize protective antibody titers for both mother and neonate,” says co–senior author Galit Alter, PhD, a core member at the Ragon Institute of MGH, MIT and Harvard and a professor of Medicine at Harvard Medical School.

The investigators stressed the need for more research on this topic. “Additional studies are needed to understand how to optimize maternal and neonatal immunity induced by vaccines in general during pregnancy,” says co–senior author Kathryn J. Gray, MD, PhD, an associate obstetrician at Brigham and Women’s Hospital and an assistant professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School.

Other study authors include Caroline G. Atyeo, Lydia L. Shook, Sara Brigida, Rose M. De Guzman, Stepan Demidkin, Cordelia Muir, Babatunde Akinwunmi, Arantxa Medina Baez, Maegan Sheehan, Erin McSweeney, Madeleine Burns, Ruhi Nayak, Maya K. Kumar, Chinmay D. Patel, Allison Fialkowski, Dana Cvrk, Ilona T. Goldfarb, Lael M. Yonker, Alessio Fasano, Alejandro B. Balazs, and Michal A. Elovitz.

This work was supported by the National Institutes of Health, MGH ECOR, Nancy Zimmerman, the Massachusetts Consortium on Pathogen Readiness, the Gates Foundation, and the Musk Foundation.

About the Massachusetts General Hospital
Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In August 2021, Mass General was named #5 in the U.S. News & World Report list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.

About Brigham and Women’s Hospital
Brigham and Women’s Hospital is a founding member of Mass General Brigham and a teaching affiliate of Harvard Medical School. With nearly 1,000 inpatient beds, approximately 50,000 inpatient stays, and over 2.6 million outpatient encounters annually, clinicians across the Brigham provide compassionate, high-quality care in virtually every medical and surgical specialty to patients locally, regionally, nationally and around the world. An international leader in basic, clinical, and translational research, Brigham and Women’s Hospital has nearly 5,000 scientists, including physician-investigators, renowned biomedical researchers and faculty supported by nearly $750 million in funding. The Brigham’s medical preeminence and service to the community dates to 1832, with the opening of the Boston Lying In, one of the nation's first maternity hospitals designed to care for women unable to afford in-home medical care. Its merger with the Free Hospital for Women resulted in the Boston Hospital for Women in 1966. In 1980, the Boston Hospital for Women, the Peter Bent Brigham Hospital and the Robert Breck Brigham Hospital officially merged to become Brigham and Women’s Hospital. With nearly 21,000 employees across the Brigham family – including the Brigham and Women’s Physicians Organization and Brigham and Women’s Faulkner Hospital – that rich history is the foundation for our commitment to providing superb care for some of the most complex cases, pursuing breakthroughs in biomedical research, training the next generation of health care providers, and serving the local and global community.