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Association of Human Milk Antibody Induction, Persistence, and Neutralizing Capacity With SARS-CoV-2 Infection vs mRNA Vaccination

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  How does human milk antibody composition and neutralization activity differ between lactating parents with COVID-19 infection vs those with COVID-19 messenger RNA vaccination?

Findings  In this cohort study of a convenience sample of 47 lactating parents with infection and 30 lactating parents who were vaccinated, antibody response in milk after infection was IgA dominant and highly variable while vaccination was associated with a robust IgG response, which began to decline by 90 days after the second vaccine dose. Milk from both groups showed neutralization activity against live SARS-CoV-2 virus, which can be attributed to IgA and IgG SARS-CoV-2 antibodies.

Meaning  COVID-19 infection and vaccination may result in significant antibodies in human milk that exhibit different temporal patterns, but both neutralize live SARS-CoV-2 virus.

Abstract

Importance  Long-term effect of parental COVID-19 infection vs vaccination on human milk antibody composition and functional activity remains unclear.

Objective  To compare temporal IgA and IgG response in human milk and microneutralization activity against SARS-CoV-2 between lactating parents with infection and vaccinated lactating parents out to 90 days after infection or vaccination.

Design, Setting, and Participants  Convenience sampling observational cohort (recruited July to December 2020) of lactating parents with infection with human milk samples collected at days 0 (within 14 days of diagnosis), 3, 7, 10, 28, and 90. The observational cohort included vaccinated lactating parents with human milk collected prevaccination, 18 days after the first dose, and 18 and 90 days after the second dose.

Exposures  COVID-19 infection diagnosed by polymerase chain reaction within 14 days of consent or receipt of messenger RNA (mRNA) COVID-19 vaccine (BNT162b2 or mRNA-1273).

Main Outcomes and Measures  Human milk anti–SARS-CoV-2 receptor-binding domain IgA and IgG and microneutralization activity against live SARS-CoV-2 virus.

Results  Of 77 individuals, 47 (61.0%) were in the infection group (mean [SD] age, 29.9 [4.4] years), and 30 (39.0%) were in the vaccinated group (mean [SD] age, 33.0 [3.4] years; P = .002). The mean (SD) age of infants in the infection and vaccinated group were 3.1 (2.2) months and 7.5 (5.2) months, respectively (P < .001). Infection was associated with a variable human milk IgA and IgG receptor-binding domain–specific antibody response over time that was classified into different temporal patterns: upward trend and level trend (33 of 45 participants [73%]) and low/no response (12 of 45 participants [27%]). Infection was associated with a robust and quick IgA response in human milk that was stable out to 90 days after diagnosis. Vaccination was associated with a more uniform IgG-dominant response with concentrations increasing after each vaccine dose and beginning to decline by 90 days after the second dose. Vaccination was associated with increased human milk IgA after the first dose only (mean [SD] increase, 31.5 [32.6] antibody units). Human milk collected after infection and vaccination exhibited microneutralization activity. Microneutralization activity increased throughout time in the vaccine group only (median [IQR], 2.2 [0] before vaccine vs 10 [4.0] after the first dose; P = .003) but was higher in the infection group (median [IQR], 20 [67] at day 28) vs the vaccination group after the first-dose human milk samples (P = .002). Both IgA and non-IgA (IgG-containing) fractions of human milk from both participants with infection and those who were vaccinated exhibited microneutralization activity against SARS-CoV-2.

Conclusions and Relevance  In this cohort study of a convenience sample of lactating parents, the pattern of IgA and IgG antibodies in human milk differed between COVID-19 infection vs mRNA vaccination out to 90 days. While infection was associated with a highly variable IgA-dominant response and vaccination was associated with an IgG-dominant response, both were associated with having human milk that exhibited neutralization activity against live SARS-CoV-2 virus.

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Article Information

Corresponding Author: Kirsi Järvinen, MD, PhD, Division of Allergy and Immunology, Department of Pediatrics, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Rochester, NY 14642 (kirsi_jarvinen-seppo@urmc.rochester.edu).

Accepted for Publication: October 5, 2021.

Published Online: November 10, 2021. doi:10.1001/jamapediatrics.2021.4897

Author Contributions: Dr Järvinen had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Young and Seppo served as co–first authors.

Concept and design: Young, Seppo, Rosen-Carole, Nowak-Wegrzyn, Ferri-Huerta, Järvinen.

Acquisition, analysis, or interpretation of data: Young, Seppo, Diaz, Nowak-Wegrzyn, Cruz Vasquez, Ferri-Huerta, Nguyen-Contant, Fitzgerald, Sangster, Topham, Järvinen.

Drafting of the manuscript: Young, Seppo, Cruz Vasquez, Ferri-Huerta, Nguyen-Contant, Fitzgerald, Järvinen.

Critical revision of the manuscript for important intellectual content: Young, Seppo, Diaz, Rosen-Carole, Nowak-Wegrzyn, Cruz Vasquez, Sangster, Topham, Järvinen.

Statistical analysis: Young, Seppo, Järvinen.

Obtained funding: Young, Ferri-Huerta, Järvinen.

Administrative, technical, or material support: Seppo, Diaz, Rosen-Carole, Nowak-Wegrzyn, Cruz Vasquez, Ferri-Huerta, Nguyen-Contant, Fitzgerald, Topham, Järvinen.

Supervision: Young, Seppo, Nowak-Wegrzyn, Sangster, Järvinen.

Conflict of Interest Disclosures: Dr Young reported grants from the National Institute of Diabetes and Digestive and Kidney Diseases and the Gerber Foundation outside the submitted work during the conduct of this study. Dr Seppo reported grants from the National Institute of Allergy and Infectious Diseases (NIAD) during the conduct of the study. Dr Rosen-Carole reported grants from the National Institutes of Health during the conduct of the study. Dr Nowak-Wegrzyn reported grants from the NIAID during the conduct of the study. Dr Järvinen reported grants from the NIAID during the conduct of the study and grants from Janssen outside the submitted work. No other disclosures were reported.

Funding/Support: This work was supported by the National Institute of Allergy and Infectious Diseases (grant U01 AI131344-04S1) and in-kind support from Medela.

Role of the Funder/Sponsor: Neither funder had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank Kaili Widrick, MS, Katherine Murphy, Miranda Klein, MPH, and Elizabeth Catlin, CNM, for their technical assistance. All individuals are employees of the University of Rochester and were not compensated outside of their standard salary. We are very grateful to the families that graciously donated their time and milk to this study.

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