The current coronavirus disease 2019 (COVID-19) pandemic has brought untold devastation in its wake, with its rapid and asymptomatic spread to hundreds of millions of people the world over. Vaccines have been hailed as the way out of this situation, and a dozen or so are being rolled out in many different countries.
However, pregnancy has remained an exclusion criteria for vaccine trials, despite being a high-risk situation regarding COVID-19. A large part of the reason for this was both the uncertainty regarding the vaccine's ability to induce an immune response in pregnancy, which is an immunotolerant state and its potential adverse effects on the mother and fetus at that time.
A new paper published in the journal JAMA reveals an answer to at least one of these questions.
Lead author Ai-ris Collier said, "Our study supports the use of vaccines in pregnant and lactating individuals. The vaccine-elicited antibodies we detected in both infant cord blood and breast milk suggest that vaccinating pregnant mothers may potentially protect infants from COVID-19 infection."
Symptomatic COVID-19 in pregnancy has been associated with a higher risk of admission to the intensive care unit (ICU), mechanical ventilation and mortality, compared to age-equivalent non-pregnant women. Preterm birth and stillbirths have also been found to be higher in pregnancies complicated by COVID-19.
The lack of evidence regarding COVID-19 vaccine safety and immunogenicity in pregnancy has led to the matter of vaccination in pregnancy being left to the discretion of individual governments and healthcare organizations. For instance, the Centers for Disease Control and Prevention (CDC) say pregnant women could take the vaccine if they so wish, in consultation with their healthcare provider.
In fact, once mRNA vaccines received Emergency Use Authorization in the USA, over 11,000 pregnant women underwent vaccination.
The new study, from Beth Israel Deaconess Medical Center (BIDMC), combined obstetric and virologic specialists to assess the immunogenicity of mRNA (messenger ribonucleic acid) vaccines (either the Pfizer or Moderna vaccines) in pregnant and lactating women.
The study was carried out on 103 women aged 18-45 years, all of whom had received one of these vaccines. Of these, 30 were pregnant and 16 lactating. Controls included 57 non-pregnant non-lactating women who had received the vaccine.
In another comparison group, there were 28 women who had been infected, of whom 22 were pregnant.
Immune antibody responses were evaluated with regard to the efficiency of antibody binding to epitopes on the SARS-CoV-2 receptor-binding domain (RBD), neutralization, and functional non-neutralizing antibody production, in all three groups. The T cells' responses to vaccination and infection were also assessed.
The immune responses were evaluated against wildtype virus variant as well as the UK and South African variants of concern (VOCs), B.1.1.7 and B.1.351, respectively. These are known to be more infectious and less susceptible to immune antibodies elicited by natural infection and even by neutralizing antibodies.
High immunogenicity in pregnancy
The results show that with both vaccines, the immune responses elicited were adequate. Both antibodies and T cells were induced by two doses of the vaccines. Moreover, maternal antibodies were transferred efficiently into the fetus, as shown by their presence in both cord blood and breast milk.
Interestingly, both pregnant and non-pregnant women were found to have cross-reactive immunity against other SARS-CoV-2 VOCs. Less than one in seven women developed fever post-vaccination compared to almost half of non-pregnant women.
The median immunoglobulin G (IgG) RBD-binding antibody titer was ~15,000 in maternal serum, and ~20,000 in cord blood, in vaccinated women, vs. ~1,300 and 635, respectively, in unvaccinated women.
The titer of neutralizing antibodies (NT50) was ~1,000 in maternal serum, and 300 in cord blood, at the time of delivery. Following natural infection, the corresponding titers were 150 and 164, respectively.
Breast milk antibodies
Breast milk samples were also assessed in both cohorts, both RBD-binding and neutralizing antibodies. The same pattern was observed, with serum IgG binding titers showing a median of 25,000 and 1,600 after vaccination and infection, respectively. This corresponded to breast milk median titers of less than 100 and ~200, respectively.
IgA binding antibody titers were 800 and 150 after vaccination and infection, respectively. Similarly, breast milk IgA antibody titers were 25 and ~2,000, respectively.
Overall neutralizing activity was 75 and 150 after vaccination and infection, respectively.
T cell responses
All vaccines elicited comparable T cells responses, considering the percentage of activated CD4 T cells, CD4 central memory T cells, CD8 T cells, and CD8 central memory T cells
What are the implications?
Not only were robust antibody responses seen following vaccination in all women, whether pregnant, non-pregnant or lactating, but the elicited antibody titers were greater than those induced by natural infection as well. This agrees with earlier reports.
Antibody transfer to the fetus via the placenta and to the infant via breast milk was observed to be efficient, underlining the additional benefit of vaccination in pregnancy to the baby as well as the mother. Cross-reactive antibodies were elicited against both VOCs examined.
These findings clearly support the use of these vaccines in all women, irrespective of the presence of pregnancy.
Further large studies should examine the protection conferred by these antibodies, and the durability of the immune response, in pregnant women. Moreover, the timing of the vaccine should be examined to ensure the optimal fetal transfer of antibodies and the protection of infants against perinatal infection.