Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

SARS-CoV-2 neutralizing antibody titers in maternal blood, umbilical cord blood, and breast milk

Abstract

Objective

We quantified neutralizing SARS-CoV-2 antibody against spike protein (nAb) levels after vaccination and SARS-CoV-2 infection in maternal serum, cord blood, and breast milk and determined whether they correlate with levels of spike protein binding antibody.

Study design

Women (n = 100) were enrolled on admission for delivery. Previous SARS-CoV-2 infection was defined by anti-nucleocapsid antibodies. Levels of nAb and binding antibodies against spike receptor binding domain were measured in maternal blood, cord blood, and milk.

Results

Maternal nAb levels were higher after vaccine and infection than vaccine alone but waned rapidly. Levels of nAb in cord blood and milk correlated with maternal levels and were higher in cord blood than maternal. Spike protein binding antibody levels correlated with nAb.

Conclusion

SARS-CoV-2 vaccination near delivery may boost antibody-mediated immunity in the peripartum period. Neutralizing antibodies are passed transplacentally and into milk. Spike protein binding antibody may be a feasible proxy for nAb.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: ln(Neutralizing Ab levels) versus number of days from last exposure by exposure group.
Fig. 2: Relationship of spike antigen binding antibody levels with neutralizing antibody levels.

Similar content being viewed by others

Data availability

The datasets generated and analyzed during this study are available from the corresponding author on reasonable request.

References

  1. Panagiotakopoulos L, Myers TR, Gee J, Lipkind HS, Kharbanda EO, Ryan DS, et al. SARS-CoV-2 Infection Among Hospitalized Pregnant Women: Reasons for Admission and Pregnancy Characteristics - Eight U.S. Health Care Centers, March 1-May 30, 2020. MMWR Morb Mortal Wkly Rep. 2020;69:1355–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Smith V, Seo D, Warty R, Payne O, Salih M, Chin KL, et al. Maternal and neonatal outcomes associated with COVID-19 infection: a systematic review. PLoS One. 2020;15:e0234187.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Walker KF, O’Donoghue K, Grace N, Dorling J, Comeau JL, Li W, et al. Maternal transmission of SARS-COV-2 to the neonate, and possible routes for such transmission: a systematic review and critical analysis. BJOG. 127: 324-1336.

  4. Moore KM, Suthar MS. Comprehensive analysis of COVID-19 during pregnancy. Biochem Biophys Res Commun. 2021;538:180–6.

    Article  CAS  PubMed  Google Scholar 

  5. Medlow AG, Li JZ, Collier AY, Atyeo C, James KE, Boatin AA, et al. Assessment of maternal and neonatal SARS-CoV-2 viral load, transplacental antibody transfer and placental pathology in pregnancies During the COVID-19 pandemic. JAMA Netw Open. 2020;3:e2030455.

    Article  Google Scholar 

  6. Pace RM, Williams JE, Järvinen KM, Belfort MB, Pace CDW, Lackey KA, et al. Characterization of SARS-CoV-2 RNA, antibodies, and neutralizing capacity in milk produced by women with COVID-19. mBio. 2021;12:e03192–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Joseph NT, Dude CM, Verkerke HP, Irby LS, Dunlop AL, Patel RM, et al. Maternal antibody response, neutralizing potency, and placental antibody transfer after severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection. Obstet Gynecol. 2021;138:189–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Atyeo C, Pullen KM, Bordt EA, Fischinger S, Burke J, Michell A, et al. Compromised SARS-CoV-2-specific placental antibody transfer. Cell. 2021;184:628–642.e10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Flannery DD, Gouma S, Dhudasia MB, Mukhopadhyay S, Pfeifer MR, Woodford EC, et al. Assessment of maternal and neonatal cord blood SARS-CoV-2 antibodies and placent transfer ratios. JAMA Pediatr. 2021;175:594–600.

    Article  PubMed  Google Scholar 

  10. Wu F, Liu M, Wang A, Lu L, Wang Q, Gu C, et al. Evaluating the association of clinical characteristics with neutralizing antibody levels in patients who have recovered from mild COVID-19 in Shanghai, China. JAMA Intern Med. 2020;180:1356–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Katz MH. Neutralizing antibodies against SARS-CoV-2-important questions, unclear answers. JAMA Intern Med. 2020;180:1362.

    Article  CAS  PubMed  Google Scholar 

  12. Gray KJ, Bordt EA, Atyeo C, Deriso E, Akinwunmi B, Young N, et.al. Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study. Am J Obstet Gynecol. 2021; https://doi.org/10.1016/j.ajog.2021.03.023

  13. Collier AY, McMahan K, Yu J, Tostanoski LH, Aguayo R, Ansel J, et al. Immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women. JAMA. 2021;325:2370–80.

    Article  CAS  PubMed  Google Scholar 

  14. Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med. 2021;27:1205–11.

    Article  CAS  PubMed  Google Scholar 

  15. Stafford LS, Valcarce V, Henry M, Neu J, Parker L, Mueller M, et al. 3rd. Detection of SARS-CoV-2 IgA and IgG in human milk and breastfeeding infant stool 6 months after maternal COVID-19 vaccination. J Perinatol. 2023;43:775–81.

    Article  CAS  PubMed  Google Scholar 

  16. Cosentino M, Marino F. In response to Detection of SARS-CoV-2 IgA and IgG in human milk and breastfeeding infant stool 6 months after maternal COVID-19 vaccination [letter]. J Perinatol. 2023;43:827.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Keller-Stanislawski B, Englund JA, Kang G, Mangtani P, Neuzil K, Nohynek H, et al. Safety of immunization during pregnancy: a review of the evidence of selected inactivated and live attenuated vaccines. Vaccine. 2014;32:7057e64.

    Article  Google Scholar 

  18. Lönnerdal B. Nestle nutr inst workshop ser. Hum Milk: Bioact Proteins/Pept Funct Prop 2016;86:97–107.

    Google Scholar 

  19. Nolan LS, Parks OB, Good M. A review of the immunomodulating components of maternal breast milk and protection against necrotizing enterocolitis. Nutrients. 2019;12:14.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Huang Y, Borisov O, Kee JJ, Carpp LN, Wrin T, Cai S, et al. Calibration of two validated SARS-CoV-2 pseudovirus neutralization assays for COVID-19 vaccine evaluation. Sci Rep. 2021;11:23921.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Schuh AJ, Satheshkumar PS, Dietz S, Bull-Otterson L, Charles M, Edens C, et al. SARS-CoV-2 convalescent sera binding and neutralizing antibody concentrations compared with COVID-19 vaccine efficacy estimates against symptomatic infection. Microbiol Spectr. 2022;10:e0124722.

    Article  PubMed  Google Scholar 

  22. Shuaib W, Badaruddin IA, Mansor M, Salleh SA, Hassan MR, Lindong S, et al. SARS-CoV-2 S-RBD IgG and neutralizing antibodies among different categories of health care workers post third dose BNT162b2 mRNA COVID-19 vaccine. Hum Vaccin Immunother. 2023;19:2266931.

    Article  Google Scholar 

  23. Flannery DD, Gouma S, Dhudasia MB, Mukhopadhyay S, Pfeifer MR, Woodford EC, et al. Comparison of maternal and neonatal antibody levels after COVID-19 vaccination vs SARS-CoV-2 infection. JAMA Netw Open. 2022;5:e2240993.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Beharier O, Plitman Mayo R, Raz T, Nahum Sacks K, Schreiber L, Suissa-Cohen Y, et al. Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine. J Clin Invest. 2021;131:e150319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Govindaraj S, Cheedarla N, Cheedarla S, Irby LS, Neish AS, Roback JD, et al. COVID-19 vaccine induced poor neutralization titers for SARS-CoV-2 omicron variants in maternal and cord blood. Front Immunol. 2023;14:1211558.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Young BE, Seppo AE, Diaz N, Rosen-Carole C, Nowak-Wegrzyn A, Cruz Vasquez JM, et al. Association of human milk antibody induction, persistence, and neutralizing capacity with SARS-CoV-2 infection vs mRNA vaccination. JAMA Pediatr. 2022;176:159–68.

    Article  PubMed  Google Scholar 

  27. Szczygioł P, Łukianowski B, Kościelska-Kasprzak K, Jakuszko K, Bartoszek D, Krajewska M, et al. Antibodies in the breastmilk of COVID-19 recovered women. BMC Pregnancy Childbirth. 2022;22:635.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Golan Y, Ilala M, Li L, Gay C, Hunagund S, Lin CY, et al. Milk antibody response after 3rd COVID-19 vaccine and SARS-CoV-2 infection and implications for infant protection. iScience. 2023;26:107767.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

MK, LR, JC, BW: study design, data analysis, writing manuscript DD: data analysis, writing manuscript KS, MM: data collection, reviewing manuscript CW, CJP, TW, KC: study design, sample analysis, reviewing manuscript.

Corresponding author

Correspondence to Barry Weinberger.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khalifeh, M., Rubin, L.G., Dayya, D. et al. SARS-CoV-2 neutralizing antibody titers in maternal blood, umbilical cord blood, and breast milk. J Perinatol 44, 28–34 (2024). https://doi.org/10.1038/s41372-023-01843-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-023-01843-w

Search

Quick links