A new commentary, published as an ‘In-Press Preview’ in the Journal of Clinical Investigation, addresses the salient issue of vaccination against the coronavirus disease (COVID-19) in pregnancy and potential antibody transfer to the fetus – and provides the evidence in support of messenger RNA (mRNA) vaccine safety and efficacy for both maternal and child health.
Pregnancy is characterized by substantial changes in the immune and endocrine systems that predispose women to potential complications caused by various pathogens – including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing COVID-19 pandemic.
More specifically, pregnant women are three times more likely to be admitted to an intensive care unit after infection, with the need for ventilator support or extracorporeal membrane oxygenation, but also more likely to succumb to the disease when compared to non-infected pregnant women.
Likewise, different obstetrical complications (most notably preterm birth) are also more frequent in cases when the mother is infected with SARS-CoV-2; hence, increasing the probability of protracted health problems for both the mother and her newborn child.
COVID-19 vaccine and pregnancy
Nonetheless, due to the novel technology and (at the time) uncertain efficacy of the mRNA vaccines against COVID-19, pregnant volunteers were initially excluded from clinical trials. In light of the above effects of COVID-19 on pregnant women, many organizations and societies have begun recommending the administration of these vaccines during pregnancy.
At the moment, there is a consensus based on the evidence that COVID-19 vaccines give rise to infertility in neither women nor men. Furthermore, if administered in pregnancy, mRNA fragments from the vaccine do not cross the placenta, being consumed by muscle cells at the injection site and/or degraded following the synthesis of an encoded protein.
However, albeit reassuring, data pertaining to pregnancy and fetal transfer are still limited. This is the reason why a research group, led by Dr. Ofer Beharier from the Hadassah-Hebrew University Medical Center in Jerusalem, decided to appraise maternal and neonatal responses to the Pfizer BNT162b2 SARS-CoV-2 mRNA vaccine.
A multicenter study in Israel
In this multicenter study, the researchers have examined a cohort of 1,094 participants from eight hospitals across Israel. Pregnant women that had an active maternal COVID-19 disease at delivery were excluded from the study, while eligibility criteria included age of 18 years (or older) and stated willingness to participate with informed consent.
Blood samples from women and umbilical cord blood samples from newborns were collected between April 2020 and March 2021. The samples were centrifuged at room temperature (1000 g for 10 minutes), and then sera were aliquoted into dedicated precoded tubes. Finally, samples were stored at -80 °C until the analysis.
All study participants were assigned into three groups: those who got the vaccine, unvaccinated ones with prior positive SARS-CoV-2 test, and those that were unvaccinated without prior infection. Titers of IgG and IgM antibodies from the sera were measured with the use of Milliplex MAP SARS-CoV-2 Antigen Panel.
Robust protection for mother and child
The study has shown a steadfast increase in maternal IgG humoral response against various components of SARS-CoV-2 spike glycoprotein in non-infected patients upon vaccination. These immunoglobulins were easily transferred to the fetus across the placenta, which led to a substantial anti-SARS-CoV-2 antibody titer in the bloodstream of neonates within 14 days of the first vaccine dose.
Furthermore, in women recovering from SARS-CoV-2 infection that has been contracted in the second trimester (i.e., 13-26 weeks of gestation), anti-COVID-19 antibodies in both maternal and cord blood samples remained elevated high at delivery.
Compared to natural infection, the vaccination generates powerful protective antibodies in women, which are successfully transferred to fetuses during pregnancy. Importantly, there was no evidence of fetal IgM response to any of the vaccine-induced antigens, which implies there was no direct exposure of the fetus to vaccine-derived antigens.
Implications and future studies
Due to the considerable burden of COVID-19 throughout pregnancy on the mother, vaccinations at any time of gestation should be considered for the benefit of maternal health. However, the vaccination of previously infected pregnant women should be based on titer testing.
Even though vaccination in very early pregnancy might result in lower efficiency of antibody transfer from mother to fetus, this should not be a reason against endorsing vaccination at any time during the gestation period, as vaccination in pregnancy obviously confers separate benefits to the mother and her fetus.
In any case, since we are dealing with vulnerable populations, more public health efforts should be put behind this concept. Future studies will also be needed to address this issue in more depth since ethnicity and race can influence adverse pregnancy outcomes with SARS-Cov2 infection.