The IgA in milk induced by SARS-CoV-2 infection is comprised of mainly secretory antibody that is neutralizing and highly durable over time
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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 (IC 50 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.
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Veronique Demers-Mathieu
Review 2: "The Spike-specific IgA in milk commonly-elicited after SARS-Cov-2 infection is concurrent with a robust secretory antibody response, exhibits neutralization potency strongly correlated with IgA binding, and is highly durable over time"
This study finds SARS-CoV-2 infection elicits a SARS-CoV-2 IgA Ab response detectable in breastmilk and these antibodies demonstrate neutralizing activity against SARS-CoV-2. Reviewers deem these findings reliable but request more detailed descriptions of the study design.
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Talat Kilic
Review 1: "The Spike-specific IgA in milk commonly-elicited after SARS-Cov-2 infection is concurrent with a robust secretory antibody response, exhibits neutralization potency strongly correlated with IgA binding, and is highly durable over time"
This study finds SARS-CoV-2 infection elicits a SARS-CoV-2 IgA Ab response detectable in breastmilk and these antibodies demonstrate neutralizing activity against SARS-CoV-2. Reviewers deem these findings reliable but request more detailed descriptions of the study design.
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Strength of evidence
Reviewers: Talat Kilic (Inonu University) | 📘📘📘📘📘
Veronique Demers-Mathieu (Medolac Laboratories) | 📒📒📒◻️◻️ -
SciScore for 10.1101/2021.03.16.21253731: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: This study was approved by the Institutional Review Board (IRB) at Mount Sinai Hospital (IRB Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Briefly, pseudovirus was produced by transfection of 293T cells with SARS-CoV-2 Spike plasmid, followed 8 h later by infection with a VSVΔG-rLuc reporter virus. 293Tsuggested: NCBI_Iran Cat# C498, RRID:CVCL_0063)Software and Algorithms Sentences Resources All statistical tests were performed in GraphPad Prism, were 2-tailed, and significance level was … SciScore for 10.1101/2021.03.16.21253731: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: This study was approved by the Institutional Review Board (IRB) at Mount Sinai Hospital (IRB Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Briefly, pseudovirus was produced by transfection of 293T cells with SARS-CoV-2 Spike plasmid, followed 8 h later by infection with a VSVΔG-rLuc reporter virus. 293Tsuggested: NCBI_Iran Cat# C498, RRID:CVCL_0063)Software and Algorithms Sentences Resources All statistical tests were performed in GraphPad Prism, were 2-tailed, and significance level was set at p-values < 0.05. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a protocol registration statement.
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