Study assesses human milk antibodies against common human coronaviruses following COVID-19 infection and vaccination

A recent study posted to the medRxiv* preprint server demonstrated that coronavirus disease 2019 (COVID-19) and its vaccination generates cross-reactive antibodies against human coronaviruses (HCoVs) in lactating mothers.

Study: Broad Cross-reactive IgA and IgG Against Human Coronaviruses in Milk Induced by COVID-19 Vaccination and Infection. Image Credit: Krysja/Shutterstock
Study: Broad Cross-reactive IgA and IgG Against Human Coronaviruses in Milk Induced by COVID-19 Vaccination and Infection. Image Credit: Krysja/Shutterstock

Background

SARS-CoV-2 comes under the zoonotic coronaviridae family. Presently, the most successful means to prevent COVID-19 and its transmission is via SARS-CoV-2 vaccination. People with symptomatic SARS-CoV-2 infection demonstrate a broad range of anti-SARS-CoV-2 antibodies. Human milk (HM) protects newborns from numerous infectious illnesses, including respiratory infections, via passive transplacental transmission of maternal antibodies. 

In addition, antibody cross-reactivity between distinct viral variants is a key source of protection against emerging viral strains. Vaccination against a novel viral strain might improve cross-reactive immunity against previously circulating variants. For SARS-CoV-2, this appears to be true since pre-pandemic HM samples were found to have a low degree of cross-reactivity with the SARS-CoV-2 receptor-binding domain (RBD) subunit.

However, it is presently unknown whether messenger ribonucleic acid (mRNA)-based COVID-19 vaccination or SARS-CoV-2 infection generates immunoglobulin A (IgA) and IgG targeting common HCoVs in nursing mothers.

About the study 

In the present study, the scientists prospectively evaluated blood and HM samples from breastfeeding women to quantify the temporal profile of IgG and IgA responses specific towards SARS-CoV-2 and their cross-reactivity against HCoVs. There were two study groups: 1) 30 lactating mothers who received mRNA-based COVID-19 vaccines such as BNT162b2 or mRNA-1273, termed vaccination cohort, and 2) 45 nursing mothers with SARS-CoV-2 infection, designated as infection cohort. Lactating women with COVID-19 were recruited between zero and 14 days following the SARS-CoV-2 diagnosis.

Before enrollment in the study, all participants submitted informed consent. Other HCoVs evaluated include NL63, SARS-CoV-1, 229E, HKU1, and OC43. Longitudinal fingerstick blood and HM samples were procured before and after SARS-CoV-2 vaccination or, for infection cohort, at five timestamps between 14 to 28 days following confirmed COVID-19 diagnosis. The anti-nucleocapsid (N) and anti-Spike (S) IgG and IgA antibody levels against HCoVs and SARS-CoV-2 were quantified using a multiplex immunoassay (mPlex-CoV). 

Findings

The results demonstrated that COVID-19 vaccination dramatically raised the anti-S IgG and IgA levels in HM. The anti-SARS-CoV-2 antibodies in blood and HM substantially increased upon 18 days of the first dose of SARS-CoV-2 mRNA-based vaccination. By contrast, while IgG levels surged following the second COVID-19 vaccine dose in HM and blood, IgA levels in HM and blood began to decline or remained constant. This hike of IgG in blood and HM was present until 187 days of the second dose COVID-19 vaccination. 

In addition, the anti-SARS-CoV-2 S2 IgGs did not elevate as high as the IgG antibodies targeting RBD, full-S, and S1 subregions. As predicted, after vaccination, no N-specific antibodies were observed. Furthermore, anti-S IgG levels in the blood and HM were strongly associated, but anti-S IgA levels were not. This observation was congruent with the authors' prior study and indicates that serum and milk IgGs have a common source, whereas distinct sources exist for milk and serum IgAs. 

Acute SARS-CoV-2 infection-induced anti-S IgA and IgG demonstrated substantially higher correlations among blood and HM than COVID-19 vaccination. COVID-19 dramatically increased anti-N IgG and IgA antibodies in HM. The increase of anti-N IgA was more consistent than anti-S IgA in HM. By contrast, anti-S IgG levels were much greater than anti-N IgG concentrations in HM. While anti-S and anti-N IgG levels continued to hike from enrollment to 28 days, IgA levels stayed constant.

SARS-CoV-2 infection and vaccination increased the number of widely cross-reactive IgG antibodies targeting HCoVs in blood and HM much more than IgA antibodies. Furthermore, a higher cross-reactivity of IgG in HM was observed compared to blood. This suggests that SARS-CoV-2 infection and vaccination may confer passive protection via HM for breastfed babies against SARS-CoV-2 and common HCoVs.

Conclusions

According to the authors, this was the first study evaluating milk anti-N IgG and IgA concentrations in SARS-CoV-2-infected nursing mothers. The study findings indicated that anti-SARS-CoV-2 S IgG and IgA levels in milk and blood were increased following mRNA-based COVID-19 vaccination and SARS-CoV-2 infection. When compared to mRNA-based COVID-19 vaccination, IgG and IgA antibody levels in milk were more closely connected with antibody levels in the blood following the SARS-CoV-2 infection. Both SARS-CoV-2 vaccination and infection resulted in higher IgG levels against common seasonal β-CoVs. This shows that SARS-CoV-2 infection or vaccination in a breastfeeding mother might lead to passive protection for the recipient newborn against COVID-19 and seasonal CoVs.

*Important notice

medRxiv 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.

Journal reference:
Shanet Susan Alex

Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.

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