COVID-19 vaccine pregnant women
Safety Assessment
Regina Kelder

Is the COVID Vaccine Safe for Pregnant Women?

An animal study offers some reassuring data

The world ushered in 2021 knowing that highly effective vaccines to fight SARS-CoV-2 were not only possible but in circulation. But six months earlier, with cases and deaths escalating at a frightening pace, vaccine success was not assured. It was around that time that Charles River’s Safety Assessment site in Lyon, France began conducting preclinical development and reproductive toxicology (DART) tests on Pfizer/BioNTech’s mRNA vaccine, one of the frontrunners in the vaccine hunt and today one of a handful of commercially available vaccines. The animal study was designed to answer important questions about whether the COVID vaccine would be safe for pregnant women, a group that is particularly vulnerable to illness from SARS-CoV-2.

Since the pandemic erupted in early 2020, some studies have shown that pregnancy is associated with more severe disease among women who have symptomatic COVID-19 compared to women who are not expecting, while fatality rates from SARS-CoV-2 among pregnant women have been reported to be nearly 14 times higher than similarly aged individuals who are not pregnant. A safe and effective vaccine could be one way to reduce morbidity and mortality.

Under extremely tight timetables, a large team of toxicologists from Lyon evaluated the Pfizer/BioNTech vaccine in Wistar rats. The females were dosed with the Pfizer/BioNTech vaccine prior to mating and during gestation and the animals were then checked for the presence of neutralizing antibodies, evidence that the animals had reacted to the vaccine. Findings from the study, which included authors from Pfizer, BioNTech, and Charles River, were published last year in the journal Reproductive Toxicology .

Eureka spoke recently with Marie Bouressam, PhD, a Research Scientist at Charles River and a co-author on the paper who served as Study Director on the project. This is part of Eureka’s ongoing series, Research Notes, which highlights recently published work of our scientists.

Q: Why is it important for any vaccine developer looking to market their vaccine to do a DART study?

MB: Drug developers are required to perform a reproductive toxicology study in order to receive regulatory approval to market their product to women of childbearing potential and pregnant and lactating women. The one we completed for BioNTech and Pfizer was designed to cover mating, pregnancy and lactation. That work is what we describe in the journal article recently published. The aim of the study was to evaluate the effects of vaccine candidates on fertility, pre- and postnatal development in the female rat and the concomitant immune response. We do this by dosing female rats with the vaccine twice prior to mating, mate the females with untreated males, and then dose the female rats twice during pregnancy. So, a total of four shots, two before gestation and two during gestation. There were two cohorts in the study. The first cohort were subject to Cesarean section and full fetal examination at the end of the gestation. The second cohort delivered naturally, and we followed those animals up to the end of the lactation period to monitor postnatal survival, growth, physical development and neurofunctional development in the offspring. In total, we followed the rats for up to twelve weeks.

Q: Were the Wistar rats from Charles River?

MB: Yes, we are lucky in Lyon because our campus has both a Research Models unit and a Safety Assessment unit. The rats literally came from across the road. It’s a great advantage because when we use time-mated animals we get them on the first day of gestation.

Q: What was the outcome of the DART study?

MB: We noted slight maternal findings in the pregnant rats and slight local reaction at the administration site, which in the rates was in the limb. That’s pretty common for vaccines. We also noted a slight reduction in body weight gain and food consumption just after administration of the vaccine. The rats quickly recovered after each administration. And when you look at the entire period, (i.e. before mating, during gestation and during lactation) overall, they were comparable with the controls. We characterized these effects as vaccine related, but not as an adverse effect, because overall the general health of the animals was not impacted. There was no effect of the vaccine on female mating performance and fertility.

For the cohort delivered by Cesarean section, there was no effect on any ovarian or uterine parameters and no effect on embryofetal survival. The results were comparable to our historical control data. We also performed a full fetal examination and found nothing alarming related to the vaccine. For pups, the cohort delivered naturally, there was no effect on postnatal survival, growth, physical or neurofunctional development.

Q: So, these findings really shed light on the safety of the vaccine for pregnant women.

MB: At the time of our study, we didn’t know if the vaccine would be safe for women of childbearing potential or pregnant/lactating women. Our study helped show it was safe and that there were no adverse outcomes for the mother or the offspring.

Q: What was it like for your team to be working on this project? I imagine there was a fair amount of tension but also excitement.

MB: Yeah. Obviously, the context was a bit special because it’s not every day that we get to work on a vaccine that gets marketed several months later. When we were first working on it, we didn’t know that it was going become what it became—to be one of the first vaccines accepted for emergency use. But we knew the importance of the work we were asked to do and so we had a consistent staff dedicated to the project, including a pool of technicians who did all the interventions. Everybody was really concentrating on what they were doing, as usual, and everyone made sure that we delivered the data on time, and that it was high quality data. But once everything was finished, we were able to look back and say “Wow, that’s amazing, that we were able to work on this vaccine that is now helping so many people around the world.”