¹Division of Allergy and Immunology, Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York
²Division of General Pediatrics and Neonatology, Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York
³Division of Pediatric Allergy and Immunology, Department of Pediatrics, Hassenfeld Children’s Hospital, NYU Grossman School of Medicine, New York, New York
⁴Department of Pediatrics, Gastroenterology and Nutrition, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland
⁵Now with Family Medicine Residency Program, University of Minnesota Medical Center, Minneapolis
⁶David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York

Read article on JAMA Network

Read Article Claim 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.

Claim CME

Buy This Activity

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.

References

Pace RM , Williams JE , Järvinen KM , et al. Characterization of SARS-CoV-2 RNA, antibodies, and neutralizing capacity in milk produced by women with COVID-19. mBio. 2021;12(1):e03192-20. doi:10.1128/mBio.03192-20 PubMed Google Scholar

Kumar J , Meena J , Yadav A , Kumar P . SARS-CoV-2 detection in human milk: a systematic review. J Matern Fetal Neonatal Med. 2021;1-8. doi:10.1080/14767058.2021.1882984 PubMed Google Scholar

Krogstad P , Contreras D , Ng H , et al. No evidence of infectious SARS-CoV-2 in human milk: analysis of a cohort of 110 lactating women. medRxiv. Preprint posted online April 7, 2021. doi:10.1101/2021.04.05.21254897 Google Scholar

Peng S , Zhu H , Yang L , et al. A study of breastfeeding practices, SARS-CoV-2 and its antibodies in the breast milk of mothers confirmed with COVID-19. Lancet Reg Health West Pac. Published online November 4, 2020. doi:10.1016/j.lanwpc.2020.100045 Google Scholar

Fox A , Marino J , Amanat F , et al. Robust and specific secretory IgA against SARS-CoV-2 detected in human milk. iScience. 2020;23(11):101735. doi:10.1016/j.isci.2020.101735 PubMed Google Scholar

Demers-Mathieu V , DaPra C , Fels S , Medo E . Receptor-binding domain severe acute respiratory syndrome coronavirus 2-specific antibodies in human milk from mothers with coronavirus disease 2019 polymerase chain reaction or with symptoms suggestive of coronavirus disease 2019. J Pediatr Gastroenterol Nutr. 2021;73(1):125-128. doi:10.1097/MPG.0000000000003158 PubMed Google Scholar Crossref

van Keulen BJ , Romijn M , Bondt A , et al. Human milk from previously COVID-19-infected mothers: the effect of pasteurization on specific antibodies and neutralization capacity. Nutrients. 2021;13(5):1645. doi:10.3390/nu13051645 PubMed Google Scholar Crossref

Center for Disease Control and Prevention. COVID-19 vaccines while pregnant or breastfeeding. Updated October 7, 2021. Accessed September 15, 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/pregnancy.html

Collier AY , McMahan K , Yu J , et al. Immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women. JAMA. 2021;325(23):2370-2380. doi:10.1001/jama.2021.7563 PubMed Google Scholar Crossref

10.

Perl SH , Uzan-Yulzari A , Klainer H , et al. SARS-CoV-2-specific antibodies in breast milk after COVID-19 vaccination of breastfeeding women. JAMA. 2021;325(19):2013-2014. doi:10.1001/jama.2021.5782 PubMed Google Scholar Crossref

11.

Kelly JC , Carter EB , Raghuraman N , et al. Anti-severe acute respiratory syndrome coronavirus 2 antibodies induced in breast milk after Pfizer-BioNTech/BNT162b2 vaccination. Am J Obstet Gynecol. 2021;225(1):101-103. doi:10.1016/j.ajog.2021.03.031 PubMed Google Scholar Crossref

12.

Gray KJ , Bordt EA , Atyeo C , et al. Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study. medRxiv. Preprint posted online September 1, 2021. doi:10.1016/j.ajog.2021.03.023 Google Scholar

13.

Juncker HG , Mulleners SJ , van Gils MJ , et al. The levels of SARS-CoV-2 specific antibodies in human milk following vaccination. J Hum Lact. 2021;37(3):477-484. doi:10.1177/08903344211027112 PubMed Google Scholar Crossref

14.

Matsuyama S , Nao N , Shirato K , et al. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad Sci U S A. 2020;117(13):7001-7003. doi:10.1073/pnas.2002589117 PubMed Google Scholar Crossref

15.

Hothorn T , Hornik K , van de Wiel M , Zeiles A . A Lego system for conditional inference. Am Stat. 2012;60:257-263. doi:10.1198/000313006X118430.Google Scholar Crossref

16.

von Elm E , Altman DG , Egger M , Pocock SJ , Gøtzsche PC , Vandenbroucke JP ; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453-1457. doi:10.1016/S0140-6736(07)61602-X PubMed Google Scholar Crossref

17.

Selma-Royo M , Bäuerl C , Mena-Tudela D , et al. Anti-Sars-Cov-2 IgA and IgG in human milk after vaccination is dependent on vaccine type and previous Sars-Cov-2 exposure: a longitudinal study. medRxiv. Preprint posted online May 23, 2021. doi:10.1101/2021.05.20.21257512 Google Scholar

18.

Sankar MJ , Sinha B , Chowdhury R , et al. Optimal breastfeeding practices and infant and child mortality: a systematic review and meta-analysis. Acta Paediatr. 2015;104(467):3-13. doi:10.1111/apa.13147 PubMed Google Scholar

19.

Horta BL , Victora CG . Short-Term Effects of Breastfeeding: a Systematic Review on the Benefits of Breastfeeding on Diarrhoea and Pneumonia Mortality. World Health Organization; 2013.

20.

Victora CG , Bahl R , Barros AJ , et al; Lancet Breastfeeding Series Group. Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet. 2016;387(10017):475-490. doi:10.1016/S0140-6736(15)01024-7 PubMed Google Scholar Crossref

21.

Manske JM . Efficacy and effectiveness of maternal influenza vaccination during pregnancy: a review of the evidence. Matern Child Health J. 2014;18(7):1599-1609. doi:10.1007/s10995-013-1399-2 PubMed Google Scholar Crossref

22.

Maertens K , De Schutter S , Braeckman T , et al. Breastfeeding after maternal immunisation during pregnancy: providing immunological protection to the newborn: a review. Vaccine. 2014;32(16):1786-1792. doi:10.1016/j.vaccine.2014.01.083 PubMed Google Scholar Crossref

23.

Schlaudecker EP , Steinhoff MC , Omer SB , et al. IgA and neutralizing antibodies to influenza a virus in human milk: a randomized trial of antenatal influenza immunization. PLoS One. 2013;8(8):e70867. doi:10.1371/journal.pone.0070867 PubMed Google Scholar

24.

Järvinen KM , Wang J , Seppo AE , Zand M . Novel multiplex assay for profiling influenza antibodies in breast milk and serum of mother-infant pairs. F1000Res. 2018;7:1822. doi:10.12688/f1000research.16717.1 PubMed Google Scholar Crossref

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

See More About

If you are not a JN Learning subscriber, you can either:

A subscription to JN Learning (CME from JAMA Network) provides:

Sign in to access

If you are not a JN Learning subscriber, you can either:

Sign in to customize your interests

With a personal account, you can:

Name Your Search

Sign in to save your search

With a personal account, you can:

Lookup An Activity

My Saved Searches

Sign in to customize your interests

With a personal account, you can:

Purchase access