In a new Journal of Reproductive Immunology study, researchers assess the protection conferred by breast milk and serum in previously infected and/or vaccinated mothers against an early SARS-CoV-2 isolate (HH-1) and the Omicron variant for newborns for up to six months after delivery.
Background
Currently, COVID-19 messenger ribonucleic acid (mRNA) vaccines are the main protective measure for children against SARS-CoV-2 infection.
The United Nations International Children’s Emergency Fund (UNICEF) has reported over 12,300 deaths in children younger than 20 years of age due to COVID-19. More specifically, 42% of these deaths were reported in children between the ages of zero and nine years. Although short-term neonatal SARS-CoV-2 infection outcomes are rare, the long-term effects of COVID-19 on neurological and physical development remain unclear.
The vertical transfer of pathogen-specific immunoglobulin G (IgG) antibodies from the mother to fetus through the placenta has been reported. Aside from the passive immunity conferred to the infant from prior infection, recent studies have similarly demonstrated that the administration of COVID-19 mRNA vaccines during pregnancy reduces the risk of hospitalization among infants younger than six months who were born to these mothers.
Breast milk consists of several immunoprotective factors, including secretory immunoglobulin A (sIgA), as well as sIgG and sIgM, which confer protection to the infant against infections. However, this form of passive immunity is not as well understood as the transfer of antibodies to the infant through the placenta.
Natural infection with SARS-CoV-2, along with BNT162b2 mRNA vaccination, during pregnancy leads to the development of neutralizing SARS-CoV-2 antibodies that are capable of binding to different regions of the viral spike protein. These antibodies are also secreted in breast milk.
In a new Journal of Reproductive Immunology study, researchers assess the protection conferred by breast milk and serum in previously infected and/or vaccinated mothers against an early SARS-CoV-2 isolate (HH-1) and the Omicron variant for newborns for up to six months after delivery.
About the study
The current German study was conducted between February 2020 and December 2021, in which a total of 21 pregnant women were included. Sixteen of the study participants had previously tested positive for COVID-19 and recovered during pregnancy. Seven of the study participants had received at least one dose of the BNT162b2 mRNA vaccine.
Study participants who recovered from COVID-19 were referred to as the ‘R group,’ while those who have recovered from COVID-19 and were vaccinated were referred to as ‘RV group.’ Five pregnant women who had received two doses of the BNT162b2 vaccine and had not been infected with SARS-CoV-2 were referred to as ‘V group .’
Blood and breast milk samples were collected from the women during lactation for a maximum of six months post-delivery. The humoral response to natural infection and/or vaccination was evaluated by qualitative anti-SARS-CoV-2 IgA enzyme-linked immunosorbent assay (ELISA), quantitative anti-S1-RBD-SARS-CoV-2 assay, and anti- SARS-CoV-2 TrimericS IgG assay. Neutralization assays using Omicron and HH-1 isolates were also conducted.
Study findings
The median age of all study participants was 36 years. A total of 16 study participants had previously been infected with SARS-CoV-2, two of whom had experienced severe COVID-19. Of those who had received one or two doses of the Pfizer-BioNTech BNT162b2 COVID-19 vaccine, no serious adverse effects were reported.
The median neutralizing antibody levels against the SARS-CoV-2 receptor binding domain (RBD) within the serum were 12,223 AU/ml, 1427 AU/ml, and 198 AU/ml for the RV, V, and R groups, respectively.
The levels of these antibodies within the breast milk were lower; however, a positive correlation was observed between serum and breast milk S1-RBD antibody levels. Similar patterns were observed for the anti-SARS-CoV-2 IgA levels within the serum and breast milk.
The anti-SARS-CoV-2 TrimericS IgG assay revealed median IgG levels of 6,860 BAU/ml, 704 BAU/ml, and 159 BAU/ml for the RV, V, and R groups, respectively. These same antibody levels within breast milk were below the detection level.
A single vaccine dose was found to increase SARS-CoV-2 specific antibody titers in breast milk. Additionally, breast milk samples with positive anti-RBD Ig neutralized both the HH-1 isolate and Omicron in vitro. However, lower antibody titers were observed against the SARS-CoV-2 Omicron variant.
Conclusions
The current study confirmed the presence of anti-SARS-CoV-2 antibodies in breast milk that were capable of neutralizing both an early pandemic SARS-CoV-2 isolate as well as the Omicron variant. Notably, mRNA vaccination improved maternal immune responses and provided passive protection in newborns.
Further studies are needed to determine the correlation that exists between maternal antibody levels and infant immune protection.
Limitations
The sample size of the current study was small. Due to the limited number of remaining breast milk samples, neutralization assays could include only eight samples. A final limitation was that the six-month follow-up analysis was not available for all the participants.
- Olearo, F., Radmanesh, L., Felber, N., et al. (2022). Anti-SARS-CoV-2 antibodies in breast milk during lactation after infection or vaccination: a cohort study. Journal of Reproductive Immunology. doi:10.1016/j.jri.2022.103685.
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