Neutralizing Activity and SARS-CoV-2 Vaccine mRNA Persistence in Serum and Breastmilk After BNT162b2 Vaccination in Lactating Women

Abstract

BackgroundThere is limited information on the functional neutralizing capabilities of breastmilk SARS-CoV-2-specific antibodies and the potential adulteration of breastmilk with vaccine mRNA after SARS-CoV-2 mRNA vaccination.MethodsWe conducted a prospective cohort study of lactating healthcare workers who received the BNT162b2 vaccine and their infants. The presence of SARS-CoV-2 neutralizing antibodies, antibody isotypes (IgG, IgA, IgM) and intact mRNA in serum and breastmilk was evaluated at multiple time points using a surrogate neutralizing assay, ELISA, and PCR, over a 6 week period of the two-dose vaccination given 21 days apart.ResultsThirty-five lactating mothers, median age 34 years (IQR 32-36), were included. All had detectable neutralizing antibodies in the serum immediately before dose 2, with significant increase in neutralizing antibody levels 7 days after this dose [median 168.4 IU/ml (IQR 100.7-288.5) compared to 2753.0 IU/ml (IQR 1627.0-4712.0), p <0.001]. Through the two vaccine doses, all mothers had detectable IgG1, IgA and IgM isotypes in their serum, with a notable increase in all three antibody isotypes after dose 2, especially IgG1 levels. Neutralizing antibodies were detected in majority of breastmilk samples a week after dose 2 [median 13.4 IU/ml (IQR 7.0-28.7)], with persistence of these antibodies up to 3 weeks after. Post the second vaccine dose, all (35/35, 100%) mothers had detectable breastmilk SARS-CoV-2 spike RBD-specific IgG1 and IgA antibody and 32/35 (88.6%) mothers with IgM. Transient, low intact vaccine mRNA levels was detected in 20/74 (27%) serum samples from 21 mothers, and 5/309 (2%) breastmilk samples from 4 mothers within 1 weeks of vaccine dose. Five infants, median age 8 months (IQR 7-16), were also recruited - none had detectable neutralizing antibodies or vaccine mRNA in their serum.ConclusionMajority of lactating mothers had detectable SARS-CoV-2 antibody isotypes and neutralizing antibodies in serum and breastmilk, especially after dose 2 of BNT162b2 vaccination. Transient, low levels of vaccine mRNA were detected in the serum of vaccinated mothers with occasional transfer to their breastmilk, but we did not detect evidence of infant sensitization. Importantly, the presence of breastmilk neutralising antibodies likely provides a foundation for passive immunisation of the breastmilk-fed infant.

Effects of Vaccination Against Influenza, Pertussis, and COVID-19 on Human Milk Antibodies: Current Evidence and Implications for Health Equity

“…Additionally, IgA levels generally peak at 14-18 days after the first dose, increase slightly for one week after the second dose, but decrease thereafter ( 96 , 102 – 105 ). In contrast to the significant increases in IgG levels after the second dose, studies have shown that IgA levels in milk do not rise further when measured > 18 days after the second dose ( 25 , 101 , 105 ).…”

“…Similar to influenza and pertussis vaccination during pregnancy ( 44 , 46 ), SARS-CoV-2 vaccination during pregnancy reduced the risk of infant hospitalization for COVID-19 up to 4-6 months of age by 30-70% ( 99 , 100 ). In contrast, infants born to mothers vaccinated after pregnancy did not have anti-SARS-CoV-2 IgG in their blood ( 25 , 101 ). However, COVID-19 vaccination during pregnancy and lactation both elicited transfer of anti-SARS-CoV-2 antibodies to human milk ( 25 , 96 , 97 , 102 – 105 ).…”

Humoral response to anti-SARS-CoV-2 vaccine in breastfeeding mothers and mother-to-infant antibody transfer through breast milk

“…Fourth, the inherent background of our IgA assay was higher than that of IgG: this technical bias has already been reported by others 16 , and could prove important for the detection of very small quantities of antibodies such as IgA in children's samples. Finally, it's important to note that antibody concentration is not always predictive of neutralizing activity, and that this can be retained by biological fluids even when small concentrations of antigen-specific antibodies are present 32 . Moreover, breast milk is a tissue rich in broadly-reacting antibodies, that might confer some degree of SARS-CoV-2 neutralization even in the absence of previous antigen exposure, as already demonstrated for other pathogens 33 .…”

Exclusive Breastfeeding and Vitamin D Supplementation: A Positive Synergistic Effect on Prevention of Childhood Infections?

“…These results supported recommendations encouraging lactating women to continue breastfeeding during and after COVID-19 illness [ 103 ]. Studies evaluating the presence of SARS-CoV-2-specific antibodies in breast milk after mRNA vaccination found that the majority of lactating mothers showed detectable neutralizing SARS-CoV-2 antibodies in breast milk, confirming possible passive immunization of breasted infants [ 104 , 105 , 106 ]. A longitudinal prospective study showed that human milk SARS-CoV-2-specific IgG levels peaked 1 month post-mRNA vaccination and persisted for at least 6 months, while SARS-CoV-2-specific IgA was detected up to 3 months but waned by 6 months.…”