Skip to main navigation menu Skip to main content Skip to site footer

Original article

Vol. 155 No. 9 (2025)

Longitudinal characterisation of immune responses in blood and breast milk and symptoms after mRNA vaccination in lactating women

Cite this as:
Swiss Med Wkly. 2025;155:4207
Published
29.09.2025

Summary

BACKGROUND: Pregnant and lactating women were systematically excluded from the first SARS-CoV-2 vaccine trials, leading to great uncertainty in those women and their treating clinicians concerning the safety of the SARS-CoV-2 vaccine [1]. Detailed information about the immune response in blood and breast milk of lactating women and the transmission to infants after mRNA vaccination against SARS-CoV-2 is still scarce.

STUDY AIMS: We aimed to characterise the antibody responses and neutralising antibody responses against different variants of SARS-CoV-2 after mRNA vaccination in blood and breast milk of lactating women. We further aimed to compare the antibody responses to a matched cohort of non-lactating women, and to identify factors associated with antibody responses. Additionally, we assessed the occurrence of post-vaccination symptoms, health status trajectories and SARS-CoV-2 infections among participants and their infants after vaccination.

METHODS: We conducted a single-centre prospective cohort study recruiting participants between October 2021 and February 2022. The study participants were recruited directly on-site at the reference vaccination centre of the Canton of Zurich, or referred to the study centre by external healthcare providers. Eligible participants were aged >18 years and had not previously been vaccinated against SARS-CoV-2 with an mRNA vaccine. The primary outcome was the antibody response (anti-S IgA, anti-S IgG, anti-N IgG) in blood plasma and breast milk in lactating women at baseline, 4 weeks and 6 weeks. Secondary outcomes were neutralising antibody responses in blood plasma at 6 weeks, as well as self-reported post-vaccination symptoms, health status (assessed using the EuroQol visual analogue scale [EQ VAS]) and SARS-CoV-2 infections in mothers and infants over the study follow-up. Antibody responses in plasma were compared with a propensity score-matched sample of non-lactating women from the population-based Zurich SARS-CoV-2 Vaccination Cohort. Descriptive statistical analyses were conducted for all outcomes, and associations between demographic and clinical factors with antibody responses were evaluated using multivariable mixed linear regression models.

RESULTS: Of 45 eligible study participants, 40 lactating women completed at least two immunological assessments and were included in analyses. Study participants had a mean age of 34.9 years and 5 (12.8%, 5/39) participants reported a prior SARS-CoV-2 infection.Two weeks after the second vaccination (at 6 weeks), all study participants tested seropositive in blood plasma for anti-S IgG and anti-S IgA, with 3 (7.7%, 3/39) testing seropositive for anti-N IgG. Neutralising antibodies against the wildtype, delta and omicron variants were detected in blood plasma of 100% (40/40), 97.4% (39/40) and 64.1% (26/40) of participants, respectively. All breast milk samples tested positive for anti-S IgG, but only 15.6% (6/40) showed detectable anti-S IgA levels. Antibody responses were similar in the matched cohort of non-lactating women. Of the 136 post-vaccination symptoms reported in mothers and the 37 reported in infants (173 post-vaccination symptoms in total), the majority were reported to be of very mild to medium severity (87.1%, 108/124 in mothers; 93.5%, 29/31 in infants) and resolved spontaneously (70.7%, 70/99 in lactating women; 42.3%, 11/26 in infants). EQ VAS scores were high at baseline (median: 85, interquartile range [IQR]: 75.5–92) and showed a minimal decrease at weeks 4 and 6 (medians: 82 and 81), with self-reported wellbeing returning to baseline levels by month 6. Over six months, 52% of the study participants reached for full follow-up (13/25) reported an infection with SARS-CoV-2, all of mild severity.

CONCLUSIONS: Antibody responses against SARS-CoV-2 in blood plasma and breast milk were found to be anti-S IgG-dominant, and neutralisation assays at 6 months showed high neutralisation capacity for the wildtype and delta variants in plasma. No difference between lactating and non-lactating women was found. Self-reported post-vaccination symptoms were mostly of medium severity, and health status returned to baseline levels by 6 months after a short-term decrease around 4–6 weeks. Mild infections were reported after vaccination.

References

  1. 1. Modi N, Ayres-de-Campos D, Bancalari E, Benders M, Briana D, Di Renzo GC, et al. Equity in coronavirus disease 2019 vaccine development and deployment. Am J Obstet Gynecol. 2021 May;224(5):423–7. 10.1016/j.ajog.2021.01.006
  2. 2. Atyeo C, Alter G. The multifaceted roles of breast milk antibodies [Cited]. Cell. 2021 Mar;184(6):1486–99. 10.1016/j.cell.2021.02.031
  3. 3. Marchand G, Patil AS, Masoud AT, Ware K, King A, Ruther S, et al. Systematic review and meta-analysis of COVID-19 maternal and neonatal clinical features and pregnancy outcomes up to June 3, 2021. AJOG Glob Rep. 2022 Feb;2(1):100049. 10.1016/j.xagr.2021.100049
  4. 4. Allotey J, Stallings E, Bonet M, Yap M, Chatterjee S, Kew T, et al.; for PregCOV-19 Living Systematic Review Consortium. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis [Cited]. BMJ. 2020 Sep;370:m3320. 10.1136/bmj.m3320
  5. 5. Hamid S, Woodworth K, Pham H, Milucky J, Chai SJ, Kawasaki B, et al.; COVID-NET Surveillance Team. COVID-19-Associated Hospitalizations Among U.S. Infants Aged <6 Months - COVID-NET, 13 States, June 2021-August 2022. MMWR Morb Mortal Wkly Rep. 2022 Nov;71(45):1442–8. 10.15585/mmwr.mm7145a3
  6. 6. Perez SE, Luna Centeno LD, Cheng WA, Marentes Ruiz CJ, Lee Y, Congrave-Wilson Z, et al. Human Milk SARS-CoV-2 Antibodies up to 6 Months After Vaccination. Pediatrics. 2022 Feb;149(2):e2021054260. 10.1542/peds.2021-054260
  7. 7. 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 Aug;26(10):107767. 10.1016/j.isci.2023.107767
  8. 8. Gonçalves J, Juliano AM, Charepe N, Alenquer M, Athayde D, Ferreira F, et al. Secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon mRNA vaccination. Cell Rep Med. 2021 Dec;2(12):100468. 10.1016/j.xcrm.2021.100468
  9. 9. 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 Feb;176(2):159–68. 10.1001/jamapediatrics.2021.4897
  10. 10. Narayanaswamy V, Pentecost BT, Schoen CN, Alfandari D, Schneider SS, Baker R, et al. Neutralizing Antibodies and Cytokines in Breast Milk After Coronavirus Disease 2019 (COVID-19) mRNA Vaccination. Obstet Gynecol. 2022 Feb;139(2):181–91. 10.1097/AOG.0000000000004661
  11. 11. Rosenberg-Friedman M, Kigel A, Bahar Y, Werbner M, Alter J, Yogev Y, et al. BNT162b2 mRNA vaccine elicited antibody response in blood and milk of breastfeeding women. Nat Commun. 2021 Oct;12(1):6222. 10.1038/s41467-021-26507-1
  12. 12. Yeo KT, Chia WN, Tan CW, Ong C, Yeo JG, Zhang J, et al. Neutralizing Activity and SARS-CoV-2 Vaccine mRNA Persistence in Serum and Breastmilk After BNT162b2 Vaccination in Lactating Women. Front Immunol. 2022 Jan;12:783975. 10.3389/fimmu.2021.783975
  13. 13. Lechosa-Muñiz C, Paz-Zulueta M, Mendez-Legaza JM, Irure-Ventura J, Cuesta González R, Calvo Montes J, et al. Induction of SARS-CoV-2-Specific IgG and IgA in Serum and Milk with Different SARS-CoV-2 Vaccines in Breastfeeding Women: A Cross-Sectional Study in Northern Spain. Int J Environ Res Public Health. 2021 Aug;18(16):8831. 10.3390/ijerph18168831
  14. 14. Charepe N, Gonçalves J, Juliano AM, Lopes DG, Canhão H, Soares H, et al. COVID-19 mRNA vaccine and antibody response in lactating women: a prospective cohort study. BMC Pregnancy Childbirth. 2021 Sep;21(1):632. 10.1186/s12884-021-04051-6
  15. 15. Jakuszko K, Kościelska-Kasprzak K, Żabińska M, Bartoszek D, Poznański P, Rukasz D, et al. Immune Response to Vaccination against COVID-19 in Breastfeeding Health Workers. Vaccines (Basel). 2021 Jun;9(6):663. 10.3390/vaccines9060663
  16. 16. 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 Jun;325(23):2370–80. 10.1001/jama.2021.7563
  17. 17. Shook LL, Fallah PN, Silberman JN, Edlow AG. COVID-19 Vaccination in Pregnancy and Lactation: Current Research and Gaps in Understanding. Front Cell Infect Microbiol. 2021 Sep;11:735394. 10.3389/fcimb.2021.735394
  18. 18. Bertrand K, Honerkamp-Smith G, Chambers CD. Maternal and Child Outcomes Reported by Breastfeeding Women Following Messenger RNA COVID-19 Vaccination. Breastfeed Med. 2021 Sep;16(9):697–701. 10.1089/bfm.2021.0169
  19. 19. Low JM, Gu Y, Ng MS, Amin Z, Lee LY, Ng YP, et al. Codominant IgG and IgA expression with minimal vaccine mRNA in milk of BNT162b2 vaccinees. NPJ Vaccines. 2021 Aug;6(1):105. 10.1038/s41541-021-00370-z
  20. 20. McLaurin-Jiang S, Garner CD, Krutsch K, Hale TW. Maternal and Child Symptoms Following COVID-19 Vaccination Among Breastfeeding Mothers. Breastfeed Med. 2021 Sep;16(9):702–9. 10.1089/bfm.2021.0079
  21. 21. Stafford LS, Valcarce V, Henry M, Neu J, Parker L, Mueller M, et al. Detection of SARS-CoV-2 IgA and IgG in human milk and breastfeeding infant stool 6 months after maternal COVID-19 vaccination. J Perinatol Off J Calif Perinat Assoc.; 2023. 10.1038/s41372-022-01581-5
  22. 22. Golan Y, Prahl M, Cassidy AG, Gay C, Wu AH, Jigmeddagva U, et al. COVID-19 mRNA Vaccination in Lactation: Assessment of Adverse Events and Vaccine Related Antibodies in Mother-Infant Dyads. Front Immunol. 2021 Nov;12:777103. 10.3389/fimmu.2021.777103
  23. 23. CoVariants [Internet] [cited 2023 Apr 17]. Available from https://covariants.org/
  24. 24. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377–81. 10.1016/j.jbi.2008.08.010
  25. 25. Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol Group. Ann Med. 2001 Jul;33(5):337–43. 10.3109/07853890109002087
  26. 26. Frei A, Kaufmann M, Amati R, Dettwiler AB, von Wyl V, Annoni AM, et al. Development of hybrid immunity during a period of high incidence of infections with Omicron subvariants: A prospective population based multi-region cohort study. medRxiv. 2022;2022.10.14.22281076. doi: https://doi.org/10.1101/2022.10.14.22281076
  27. 27. Menges D, Zens KD, Ballouz T, Caduff N, Llanas-Cornejo D, Aschmann HE, et al. Heterogenous humoral and cellular immune responses with distinct trajectories post-SARS-CoV-2 infection in a population-based cohort. Nat Commun. 2022 Aug;13(1):4855. 10.1038/s41467-022-32573-w
  28. 28. Fenwick C, Croxatto A, Coste AT, Pojer F, André C, Pellaton C, et al. Changes in SARS-CoV-2 Spike versus Nucleoprotein Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence Studies. J Virol. 2021 Jan;95(3):e01828-20. 10.1128/JVI.01828-20
  29. 29. Fenwick C, Turelli P, Pellaton C, Farina A, Campos J, Raclot C, et al. A high-throughput cell- and virus-free assay shows reduced neutralization of SARS-CoV-2 variants by COVID-19 convalescent plasma. Sci Transl Med. 2021 Aug;13(605):eabi8452. 10.1126/scitranslmed.abi8452
  30. 30. Bürzle O, Menges D, Maier JD, Schams D, Puhan MA, Fehr J, et al. Adverse effects, perceptions and attitudes related to BNT162b2, mRNA-1273 or JNJ-78436735 SARS-CoV-2 vaccines: population-based cohort. NPJ Vaccines. 2023 Apr;8(1):61. 10.1038/s41541-023-00657-3
  31. 31. Wei J, Stoesser N, Matthews PC, Ayoubkhani D, Studley R, Bell I, et al.; COVID-19 Infection Survey team. Antibody responses to SARS-CoV-2 vaccines in 45,965 adults from the general population of the United Kingdom. Nat Microbiol. 2021 Sep;6(9):1140–9. 10.1038/s41564-021-00947-3
  32. 32. Shrotri M, Fragaszy E, Nguyen V, Navaratnam AM, Geismar C, Beale S, et al. Spike-antibody responses to COVID-19 vaccination by demographic and clinical factors in a prospective community cohort study. Nat Commun. 2022 Oct;13(1):5780. 10.1038/s41467-022-33550-z
  33. 33. Pellini R, Venuti A, Pimpinelli F, Abril E, Blandino G, Campo F, et al. Initial observations on age, gender, BMI and hypertension in antibody responses to SARS-CoV-2 BNT162b2 vaccine [Internet]. EClinicalMedicine. 2021 Jun;36:100928. [cited 2025 May 18] 10.1016/j.eclinm.2021.100928
  34. 34. Notarte KI, Ver AT, Velasco JV, Pastrana A, Catahay JA, Salvagno GL, et al. Effects of age, sex, serostatus, and underlying comorbidities on humoral response post-SARS-CoV-2 Pfizer-BioNTech mRNA vaccination: a systematic review. Crit Rev Clin Lab Sci. 2022 Sep;59(6):373–90. 10.1080/10408363.2022.2038539
  35. 35. Kuznetsova A, Brockhoff PB, Christensen RH. lmerTest Package: Tests in Linear Mixed Effects Models. J Stat Softw. 2017;82(13):1–26. doi: https://doi.org/10.18637/jss.v082.i13
  36. 36. Bland M. An Introduction to Medical Statistics. 4th ed. UK: Oxford University Press; 2015.
  37. 37. R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing. Vienna, Austria 2017. [Internet] https://www.R-project.org/
  38. 38. Scrimin F, Campisciano G, Comar M, Ragazzon C, Davanzo R, Quadrifoglio M, et al. IgG and IgA Antibodies Post SARS-CoV-2 Vaccine in the Breast Milk and Sera of Breastfeeding Women. Vaccines (Basel). 2022 Jan;10(1):125. 10.3390/vaccines10010125
  39. 39. Atyeo C, DeRiso EA, Davis C, Bordt EA, DeGuzman RM, Shook LL, et al. COVID-19 mRNA vaccines drive differential Fc-functional profiles in pregnant, lactating, and non-pregnant women. BioRxiv Prepr Serv Biol. 2021;2021.04.04.438404. doi: 10.1101/2021.04.04.438404
  40. 40. Juncker HG, Mulleners SJ, van Gils MJ, Bijl TP, de Groot CJ, Pajkrt D, et al. Comparison of SARS-CoV-2-Specific Antibodies in Human Milk after mRNA-Based COVID-19 Vaccination and Infection. Vaccines (Basel). 2021 Dec;9(12):1475. 10.3390/vaccines9121475
  41. 41. Hunagund S, Golan Y, Asiodu IV, Prahl M, Gaw SL. Effects of Vaccination Against Influenza, Pertussis, and COVID-19 on Human Milk Antibodies: Current Evidence and Implications for Health Equity. Front Immunol. 2022 Jul;13:910383. 10.3389/fimmu.2022.910383
  42. 42. Demers-Mathieu V, Hakansson AP, Hall S, Lavangnananda S, Fels S, Medo E. Functional Antibodies Against SARS-CoV-2 Receptor Binding Domain Variants with Mutations N501Y or E484K in Human Milk from COVID-19-Vaccinated, -Recovered, and -Unvaccinated Women. Breastfeed Med. 2022 Feb;17(2):163–72. 10.1089/bfm.2021.0232
  43. 43. Nicolaidou V, Georgiou R, Christofidou M, Felekkis K, Pieri M, Papaneophytou C. Detection of SARS-CoV-2-Specific Antibodies in Human Breast Milk and Their Neutralizing Capacity after COVID-19 Vaccination: A Systematic Review. Int J Mol Sci. 2023 Feb;24(3):2957. 10.3390/ijms24032957
  44. 44. 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 Aug;138(2):189–97. 10.1097/AOG.0000000000004440
  45. 45. 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 Sep;225(3):303.e1–17. 10.1016/j.ajog.2021.03.023
  46. 46. Perl SH, Uzan-Yulzari A, Klainer H, Asiskovich L, Youngster M, Rinott E, et al. SARS-CoV-2-Specific Antibodies in Breast Milk After COVID-19 Vaccination of Breastfeeding Women. JAMA. 2021 May;325(19):2013–4. 10.1001/jama.2021.5782
  47. 47. Selma-Royo M, Bäuerl C, Mena-Tudela D, Aguilar-Camprubí L, Pérez-Cano FJ, Parra-Llorca A, 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. Genome Med. 2022 Apr;14(1):42. 10.1186/s13073-022-01043-9
  48. 48. Fox A, Marino J, Amanat F, Krammer F, Hahn-Holbrook J, Zolla-Pazner S, et al. Robust and Specific Secretory IgA Against SARS-CoV-2 Detected in Human Milk. iScience. 2020 Nov;23(11):101735. 10.1016/j.isci.2020.101735
  49. 49. Romero Ramírez DS, Lara Pérez MM, Carretero Pérez M, Suárez Hernández MI, Martín Pulido S, Pera Villacampa L, et al. SARS-CoV-2 Antibodies in Breast Milk After Vaccination. Pediatrics. 2021 Nov;148(5):e2021052286. 10.1542/peds.2021-052286
  50. 50. Kudriavtsev AV, Vakhrusheva AV, Novosеletsky VN, Bozdaganyan ME, Shaitan KV, Kirpichnikov MP, et al. Immune Escape Associated with RBD Omicron Mutations and SARS-CoV-2 Evolution Dynamics. Viruses. 2022 Jul;14(8):1603. 10.3390/v14081603
  51. 51. Schwartz A, Nir O, Toussia-Cohen S, Leibovich L, Strauss T, Asraf K, et al. Presence of SARS-CoV-2 antibodies in lactating women and their infants following BNT162b2 messenger RNA vaccine. Am J Obstet Gynecol. 2021 Nov;225(5):577–9. 10.1016/j.ajog.2021.07.016
  52. 52. Atyeo C, Shook LL, Nziza N, Deriso EA, Muir C, Baez AM, et al. COVID-19 booster dose induces robust antibody response in pregnant, lactating, and nonpregnant women. Am J Obstet Gynecol. 2023 Jan;228(1):68.e1–12. 10.1016/j.ajog.2022.07.014
  53. 53. Yang X, Fox A, DeCarlo C, Norris C, Griffin S, Wedekind S, et al. Comparative Profiles of SARS-CoV-2 Spike-Specific Human Milk Antibodies Elicited by mRNA- and Adenovirus-Based COVID-19 Vaccines. Breastfeed Med. 2022 Aug;17(8):638–46. 10.1089/bfm.2022.0019
  54. 54. Juncker HG, Mulleners SJ, Ruhé EJ, Coenen ER, Bakker S, van Doesburg M, et al. Comparing the human milk antibody response after vaccination with four COVID-19 vaccines: A prospective, longitudinal cohort study in the Netherlands. EClinicalMedicine. 2022 May;47:101393. 10.1016/j.eclinm.2022.101393
  55. 55. Trofin F, Nastase EV, Iancu LS, Constantinescu D, Cianga CM, Lunca C, et al. Anti-RBD IgA and IgG Response and Transmission in Breast Milk of Anti-SARS-CoV-2 Vaccinated Mothers. Pathogens. 2022 Feb;11(3):286. 10.3390/pathogens11030286
  56. 56. Scourfield DO, Reed SG, Quastel M, Alderson J, Bart VM, Teijeira Crespo A, et al.; Oxford-Cardiff COVID-19 Literature Consortium. The role and uses of antibodies in COVID-19 infections: a living review. Oxf Open Immunol. 2021 Jan;2(1):iqab003. 10.1093/oxfimm/iqab003
  57. 57. Romero Ramírez DS, Suárez Hernández MI, Fernández Vilar AM, Rivero Falero M, Reyes Millán B, González Carretero P, et al. Evaluation of Adverse Effects in Nursing Mothers and Their Infants After COVID-19 mRNA Vaccination. Breastfeed Med. 2022 May;17(5):412–21. 10.1089/bfm.2021.0256
  58. 58. Lagebeurteilung E. 3. Januar 2022 – Swiss National COVID-19 Science Task Force [Internet]. [cited 2023 Apr 25]. Available from: https://sciencetaskforce.ch/epidemiologische-lagebeurteilung-3-januar-2022/
  59. 59. Moderna COVID-19 Vaccine’s Reactions and Adverse Events | CDC [Internet]. 2022 [cited 2023 May 22]. Available from: https://www.cdc.gov/vaccines/covid-19/info-by-product/moderna/reactogenicity.html
  60. 60. Pfizer-BioNTech COVID-19 Vaccine Reactions & Adverse Events | CDC [Internet]. 2023 [cited 2023 May 22]. Available from: https://www.cdc.gov/vaccines/covid-19/info-by-product/pfizer/reactogenicity.html
  61. 61. Sathian B, Asim M, Banerjee I, Pizarro AB, Roy B, van Teijlingen ER, et al. Impact of COVID-19 on clinical trials and clinical research: A systematic review. Nepal J Epidemiol. 2020 Sep;10(3):878–87. 10.3126/nje.v10i3.31622
  62. 62. Spitzer S. Biases in health expectancies due to educational differences in survey participation of older Europeans: it’s worth weighting for. Eur J Health Econ. 2020 Jun;21(4):573–605. 10.1007/s10198-019-01152-0
  63. 63. Italianer MF, Naninck EF, Roelants JA, van der Horst GT, Reiss IK, Goudoever JB, et al. Circadian Variation in Human Milk Composition, a Systematic Review [Internet]. Nutrients. 2020 Aug;12(8):2328. 10.3390/nu12082328