The IgA in milk induced by SARS-CoV-2 infection is comprised of mainly secretory antibody that is neutralizing and highly durable over time

Alisa Fox,Fatima Amanat,Susan Zolla-Pazner,Jennifer Hahn-Holbrook,Benhur Lee,Kasopefoluwa Y. Oguntuyo,Rebecca L. Powell,Jessica Marino,Etsuro Ito

doi:10.1371/journal.pone.0249723

Alisa Fox, Fatima Amanat + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0249723

Copy DOI

Abstract

Approximately 10% of infants infected with SARS-CoV-2 will experience COVID-19 illness requiring advanced care. A potential mechanism to protect this population is passive immunization via the milk of a previously infected person. We and others have reported on the presence of SARS-CoV-2-specific antibodies in human milk. We now report the prevalence of SARS-CoV-2 IgA in the milk of 74 COVID-19-recovered participants, and find that 89% of samples are positive for Spike-specific IgA. In a subset of these samples, 95% exhibited robust IgA activity as determined by endpoint binding titer, with 50% considered high-titer. These IgA-positive samples were also positive for Spike-specific secretory antibody. Levels of IgA antibodies and secretory antibodies were shown to be strongly positively correlated. The secretory IgA response was dominant among the milk samples tested compared to the IgG response, which was present in 75% of samples and found to be of high-titer in only 13% of cases. Our IgA durability analysis using 28 paired samples, obtained 4-6 weeks and 4-10 months after infection, found that all samples exhibited persistently significant Spike-specific IgA, with 43% of donors exhibiting increasing IgA titers over time. Finally, COVID-19 and pre-pandemic control milk samples were tested for the presence of neutralizing antibodies; 6 of 8 COVID-19 samples exhibited neutralization of Spike-pseudotyped VSV (IC50 range, 2.39-89.4ug/mL) compared to 1 of 8 controls. IgA binding and neutralization capacities were found to be strongly positively correlated. These data are highly relevant to public health, not only in terms of the protective capacity of these antibodies for breastfed infants, but also for the potential use of such antibodies as a COVID-19 therapeutic, given that secretory IgA is highly in all mucosal compartments.

Highlights

Though COVID-19 pathology among children is typically more mild compared to adults, approximately 10% of infants under the age of one year experience severe COVID-19 illness requiring advanced care, and an ever-growing number of children appear to exhibit signs of “Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19” weeks or months after exposure [1, 2]
15/20 undiluted milk samples from COVID-19-recovered donors were positive for Spike-specific IgG compared to prepandemic controls (75%; Fig 2b), with 13/15 of these samples exhibiting a positive endpoint titer (87%; Fig 2d), and 2/15 designated as high titer with values 5 times cutoff (13%)
There has been no evidence that SARS-CoV-2 transmits via human milk, with sporadic cases of viral RNA detected on breast skin [14]; there have been reports of viral RNA in the milk, though collection methods in these reports did not necessarily include masking, cleaning of the breast, or even handwashing to avoid contamination from the donor’s environment

Summary

Introduction

Though COVID-19 pathology among children is typically more mild compared to adults, approximately 10% of infants under the age of one year experience severe COVID-19 illness requiring advanced care, and an ever-growing number of children appear to exhibit signs of “Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19” weeks or months after exposure [1, 2]. Infants and young children can transmit SARS-CoV-2 to others and the efficacy of vaccines available for adults have not yet been evaluated for young children or infants [3]. Protecting this population from infection is essential [4]. 90% of human milk antibody (Ab) is IgA, most in secretory (s) form (sIgA, which consists of polymeric Abs complexed to J-chain and secretory component (SC) proteins) [6]. Most sIgA derives from the gut-associated lymphoid tissue (GALT), via the entero-mammary link, though there is homing of B cells from other mucosa (e.g., from the respiratory system), and possibly drainage from local lymphatics of systemic IgA to the mammary gland [6]. It has been shown that after 2 hours in the infant stomach, the total IgA concentration decreases by 75% [8]

Methods

Results

Conclusion