Pregnant women have been excluded from large vaccine trials to date, and yet this group is more likely to become severely ill with COVID-19 and may be at increased risk for adverse pregnancy outcomes, according to the US Centers for Disease Control and Prevention.
The researchers at researchers at Massachusetts General Hospital, Brigham and Women’s Hospital, and the Ragon Institute of MGH, MIT and Harvard, say their study is the largest of its kind to date.
'Two lives can be saved simultaneously with a powerful vaccine'
Published in the American Journal of Obstetrics and Gynecology this month, the study looked at Pfizer and Moderna’s vaccines across a study size of 131 women. This included 84 pregnant women (13 of whom were vaccinated during their third trimester and delivered during the study timeframe from December 2020 to March 2021), 31 lactating women and 16 non-pregnant women of reproductive age.
The vaccine-induced titers were equivalent in all three groups: while side effects after vaccination were rare and comparable across study participants, say the researchers.
The study also found that vaccinated women had ‘significantly higher’ levels of antibodies than those found in people following natural infection with COVID-19 during pregnancy.
Vaccine-generated antibodies were also present in all umbilical cord blood and breastmilk samples taken from the study, showing the transfer of antibodies from mothers to newborns.
“We now have clear evidence the COVID vaccines can induce immunity that will protect infants,” says Galit Alter, PhD, core member of the Ragon Institute and co-senior author of the study.
“We hope this study will catalyze vaccine developers to recognize the importance of studying pregnant and lactating individuals, and include them in trials.
"The potential for rational vaccine design to drive improved outcomes for mothers and infants is limitless, but developers must realize that pregnancy is a distinct immunological state, where two lives can be saved simultaneously with a powerful vaccine.
Moderna vaccine prompts higher mucosal antibodies
Comparing the Pfizer and Moderna vaccines, the study found the levels of mucosal (IgA) antibodies were higher after the second dose of Moderna compared to the second dose of Pfizer.
“This finding is important for all individuals, since SARS-CoV-2 is acquired through mucosal surfaces like the nose, mouth and eyes,” says Kathryn Gray, MD, PhD, an obstetrician at Brigham and Women’s Hospital and a first author of the paper. “But it also holds special importance for pregnant and lactating women because IgA is a key antibody present in breastmilk.”
Timing of vaccination
In the study, doses were administered across all trimesters: with the mean gestational age for the first dose at 23.3 weeks.
The researchers say that, based on what is known about other vaccines, the amount of maternal IgG transferred across the placenta to the cord is likely to differ by trimester of vaccination.
"Based on data from natural infection, qualitative changes in vaccine-elicited antibodies are likely to profoundly alter antibody transfer, and immunization with a de novo antigen earlier in pregnancy is likely to increase placental transfer.
"Understanding vaccine-induced antibody transfer kinetics across all pregnancy trimesters will be an important direction for future research.
"While timing maternal COVID-19 vaccination may not be possible during this phase of the pandemic, understanding optimal timing of vaccination to augment neonatal humoral immunity remains important. Unlike vaccines that aim to boost pre-existing antibodies (e.g influenza and pertussis vaccines), optimal timing for de novo vaccine administration remains unclear."
COVID-19 vaccines in pregnant women and children
Pfizer and BioNTech started a Phase 2/3 trial for their vaccine in pregnant women last month, with the US study set to cover 4,000 women who will be vaccinated between 24 and 34 weeks of gestation. Infants will be monitored through to six months old.
Pfizer and BioNTech also plan to launch a study in children aged 5-11 years old later this year.
AstraZeneca launched a trial for its vaccine in children aged six and over in February this year.
This month Moderna dosed the first participants in a Phase 2/3 trial in children aged 6 months to under 12 years old.
Funding for the study included grants from the National Institute of Child Health and Human Development (NICHD), the Gates Foundation, the Massachusetts Consortium on Pathogen Readiness (MassCPR) and the Musk Foundation. The researchers now plan to extend their studies to all vaccine platforms.
Source: Gray KJ, Bordt EA, Atyeo C, Deriso E, Akinwunmi B, Young N, Medina Baez A, Shook LL, Cvrk D, James K, De Guzman R, Brigida S, Diouf K, Goldfarb I, Bebell LM, Yonker LM, Fasano A, Rabi SA, Elovitz MA, Alter G, Edlow AG, COVID-19 vaccine response in pregnant and lactating women: a cohort study, American Journal of Obstetrics and Gynecology (2021), doi: https:// doi.org/10.1016/j.ajog.2021.03.023