Antibody responses engendered by maternal SARS-CoV-2 vaccination following initial and booster doses in maternal circulation and breastmilk

In a recent study posted to the bioRxiv* preprint server, researchers investigated passive immunization of the fetus and neonates by evaluating the antibody responses elicited by primary and booster doses of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination.

Background

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Although neonates are highly susceptible to infections in the early stages of life due to an immature immune system, maternal antibodies that are passively transferred to the newborn through the placenta during the pregnancy or through breastmilk after birth are thought to grant some protection during the initial stages of growth. Immunoglobulin G (IgG) is passed on from the mother to the fetus via the circulatory pathway through the placenta.

Furthermore, pregnant individuals are encouraged to get vaccinated against influenza, tetanus, diphtheria, and pertussis during gestation to ensure optimum transfer of maternal IgG to the fetus.

Evidence during the coronavirus disease 2019 (COVID-19) pandemic suggests that SARS-CoV-2 infections during pregnancy can have detrimental effects on the health of the mother and the fetus. Despite the evidence on the safety of the SARS-CoV-2 maternal vaccine, vaccine hesitancy among pregnant individuals has resulted in only 71.5% primary vaccinations and even less booster dose coverage.

For many pregnant individuals, decisions to receive or delay vaccinations depend on their understanding of the impact of the vaccine on fetal health. Therefore, it is important to longitudinally evaluate the antibody titers generated by the SARS-CoV-2 maternal vaccine to determine the benefits of maternal vaccination for the fetus's health.

About the study

In the present study, the researchers measured the antibody titers in blood, cord blood, breastmilk, and newborn blood obtained from a cohort of 121 pregnant women over the course of their gestation, birth, and up to a year after birth. The participants had received the SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccine, and 70% of the participants had also received one booster dose post-partum.

The IgG end-point titers were determined using enzyme-linked immunosorbent assays (ELISA) against the SARS-CoV-2 spike protein receptor binding domain (RBD). Specific isotypes of IgG were also measured in breastmilk and maternal, umbilical cord, and newborn plasma samples using horseradish peroxidase (HRP) anti-human immunoglobulins G1, G2, G3, and G4.

Results

The results reported that while the primary two-dose vaccination elicited appreciable levels of SARS-CoV-2 spike protein RBD-specific IgG in maternal blood, umbilical cord blood, and breastmilk, the booster dose elicited significantly higher levels of antibodies in maternal blood and breastmilk.

The levels of maternal anti-SARS-CoV-2 antibodies detected in newborn blood and cord blood were lower than those detected in maternal blood, indicating passive transplacental immunization. Furthermore, anti- SARS-CoV-2 antibody titers were inversely correlated with the time elapsed since primary maternal vaccination, with neonates of mothers vaccinated during early pregnancy having lower levels of IgG antibodies.

Since other studies had reported differences in antibody end-point titers and transplacental transfer based on the sex of the fetus, the researchers also investigated associations between fetal sex and IgG levels in maternal circulation during gestation and delivery and in neonatal plasma. No significant associations were found between the sex of the fetus and levels of IgG in maternal blood or neonatal plasma.

The longitudinal analyses that allowed the testing of IgG levels post-booster doses, and the inclusion of neonatal blood, which allowed the evaluation of passive antibody transfer, were some of the strengths of the study. However, the study was limited by the fact that only RBD-specific IgG antibodies were measured, and no other functional assays to detect the neutralization abilities of vaccine-induced antibodies were conducted.

The results suggested that while passive immunization occurs in utero through the placenta and through breastmilk after birth, antibodies elicited by the initial vaccination wane in about six months. The study highlighted the importance of booster vaccines in increasing anti-SARS-CoV-2 antibodies and ensuring the protection of the fetus through transplacental antibody transfer.

Furthermore, the authors recommended breastfeeding until the newborn is at least six months old. While the Centers for Disease Control and Prevention has approved SARS-CoV-2 vaccines for children six months old or above, breastfeeding through the first year is beneficial since maternal antibodies after the booster dose have been seen to persist in breastmilk for at least 12 months post-partum.

Conclusions

To summarize, the study evaluated the anti-SARS-CoV-2 antibody titers elicited by primary and booster doses of maternal COVID-19 vaccination in maternal blood, umbilical cord blood, neonatal blood, and breastmilk to understand the passive immunization of the fetus.

Overall, the results indicated that maternal antibodies are passively transferred to the fetus in utero via the placenta and after birth through breastmilk. Furthermore, booster doses, irrespective of the gestation stage at which the vaccination is administered, significantly elevated the antibody levels in maternal blood and breastmilk, highlighting the importance of booster doses in protecting neonates against SARS-CoV-2.

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.