SARS-CoV-2 anti-RBD immune response in breast milk from puerperal women vaccinated with Abdala

Authors

Keywords:

Abdala vaccine; IgA; IgG; neutralizing antibodies; SARS-CoV-2

Abstract

Introduction: The immune response generated in breast milk by protein subunit anti-SARS-CoV-2 vaccines, such as Abdala, was unknown.

Objective: To analyze the anti-RBD antibody response of SARS-CoV-2 in breast milk samples from postpartum women, 5 and 9 weeks after three doses of Abdala, and from unvaccinated but infected with SARS-CoV-2.

Methods: A single-center analytical observational study was carried out to semi-quantify by titration the anti-RBD IgA and IgG antibodies of the Wuhan-Hu-1 strain and the Omicron BA.5 variant, in breast milk at both post-vaccination times. The neutralizing antibody titers in vaccinated women were evaluated and compared with those generated by SARS-CoV-2 infection. Neutralizing antibody titers were correlated to the presence of chronic noncommunicable diseases, parity and age of vaccinated participants.

Results: In all breast milk samples from vaccinated women, IgA and IgG antibodies were detected against RBD-Wuhan-Hu-1 and anti-RBD-Omicron-BA.5, the latter with levels lower than those against RBD-Wuhan-Hu-1. The IgA isotype predominated over IgG. The neutralizing antibody titers were stable up to 9 weeks post-vaccination and in a magnitude similar to those generated by the infection. The presence of chronic noncommunicable diseases and multiparity correlated with the lowest titers, and these did not correlate with the age of the participants.

Conclusions: Abdala vaccine generates in breast milk, 5 and 9 weeks after three doses, different levels of IgA and IgG anti-RBD-Omicron BA.5 and anti-RBD-Wuhan-Hu-1, with neutralizing titers similar to those generated by SARS-CoV-2. Neutralizing antibody titers decreased in the presence of chronic non-communicable diseases or due to multiparity.

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References

1. Lee P, Kim CU, Seo SH, Kim DJ. Current Status of COVID-19 Vaccine Development: Focusing on Antigen Design and Clinical Trials on Later Stages. Immune Netw. 26 de febrero de 2021;21(1):e4. Disponible en: https://doi.org/10.4110/in.2021.21.e4

2. 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. 3 de febrero de 2023;24(3):2957. Disponible en: https://doi.org/10.3390/ijms24032957

3. Bian J, Li Z. Angiotensin-converting enzyme 2 (ACE2): SARS-CoV-2 receptor and RAS modulator. Acta Pharm Sin B. 1 de enero de 2021;11(1):1-12. Disponible en: https://doi.org/10.1016/j.apsb.2020.10.006

4. Del Carpio-Orantes L, Sánchez-Díaz JS, García-Méndez S, Rosas-Lozano AL, Aguilar-Silva A, Mejía-Ramos SG. Tropismo multifacético del SARS-CoV-2. Med Int Méx. 2023;39(1):108-13. Disponible en: https://doi.org/10.24245/mim.v39i1.7734

5. Limonta-Fernández M, Chinea-Santiago G, Martín-Dunn AM, González-Roche D, Bequet-Romero M, Márquez-Perera G, et al. An engineered SARS-CoV-2 receptor-binding domain produced in Pichia pastoris as a candidate vaccine antigen. New Biotechnol. 25 de diciembre de 2022;72:11-21. Disponible en: https://doi.org/10.1016/j.nbt.2022.08.002

6. COVID-19 Vaccines Advice [Internet]. [citado 12 de septiembre de 2023]. Disponible en: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines/advice

7. de Siqueira Alves Lopes A, Fontes Vieira SC, Lima Santos Porto R, Santana Santos V, Fontes Leite DC, Eduardo Cuevas L, et al. Coronavirus disease‐19 deaths among children and adolescents in an area of Northeast, Brazil: why so many? Trop Med Int Health. enero de 2021;26(1):115-9. Disponible en: https://doi.org/10.1111/tmi.13529

8. Shook LL, Atyeo CG, Yonker LM, Fasano A, Gray KJ, Alter G, et al. Durability of Anti-Spike Antibodies in Infants After Maternal COVID-19 Vaccination or Natural Infection. JAMA. 3 de marzo de 2022;327(11):1087. Disponible en: https://doi.org/10.1001/jama.2022.1206

9. Georgountzou A, Papadopoulos NG. Postnatal Innate Immune Development: From Birth to Adulthood. Front Immunol. 11 de agosto de 2017;8:957. Disponible en: https://doi.org/10.3389/fimmu.2017.00957

10. Jorgensen SCJ, Burry L, Tabbara N. Role of maternal COVID-19 vaccination in providing immunological protection to the newborn. Pharmacotherapy. enero de 2022;42(1):58-70. Disponible en: https://doi.org/10.1002/phar.2649

11. Whited N, Cervantes J. Antibodies Against SARS-CoV-2 in Human Breast Milk After Vaccination: A Systematic Review and Meta-Analysis. Breastfeed Med. 1 de junio de 2022;17(6):475-83. Disponible en: https://doi.org/10.1089/bfm.2021.0353

12. Muyldermans J, De Weerdt L, De Brabandere L, Maertens K, Tommelein E. The Effects of COVID-19 Vaccination on Lactating Women: A Systematic Review of the Literature. Front Immunol. 2022;13:852928. Disponible en: https://doi.org/10.3389/fimmu.2022.852928

13. Dimitroglou M, Sokou R, Iacovidou N, Pouliakis A, Kafalidis G, Boutsikou T, et al. Anti-SARS-CoV-2 Immunoglobulins in Human Milk after Coronavirus Disease or Vaccination—Time Frame and Duration of Detection in Human Milk and Factors That Affect Their Titers: A Systematic Review. Nutrients. 14 de abril de 2023;15(8):1905. Disponible en: https://doi.org/10.3390/nu15081905

14. Pérez-Bernal M, Hernández C, Ibargollín R, Martínez M, Soria M, Delgado M, et al. Diseño factorial completo de experimentos para optimizar un ELISA que detecta anticuerpos anti-RBD del SARS-CoV-2 en leche materna. Biotecnia. 20 de septiembre de 2023;25(3):85-92. Disponible en: https://doi.org/10.18633/biotecnia.v25i3.2012

15. Singh G. Determination of Cutoff Score for a Diagnostic Test. Internet J Lab Med. 31 de diciembre de 2006;2(1). Disponible en: https://doi.org/10.5580/1aca

16. Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale, N.J: L. Erlbaum Associates; 1988. 567 p.

17. Domínguez-Lara S. Magnitud del efecto, una guía rápida. Educ Médica. 1 de julio de 2018;19(4):251-4. Disponible en: http://dx.doi.org/10.1016/j.edumed.2017.07.002

18. Molina Arias M, Ochoa Sangrador C, Ortega Páez E. Correlación. Modelos de regresión. Evid Pediatr. 10 de junio de 2021;17:25. Disponible en: https://archivos.evidenciasenpediatria.es/DetalleArticulo/_LLP3k9qgzIh7aNQBiadwmS12kojywKGbkyhiUJp8NNvEge-jlu2inUrmk9Gqbge7bQ_Y3p-9mPn9YOIaUxNoKQ

19. Pérez-Bernal M, Hernández C, Ibargollín R, Martínez M, Soria M, Delgado M, et al. SARS-CoV-2 spike RBD-specific IgA and IgG antibodies in breast milk after vaccination with the protein subunit vaccine Abdala. Infect Med. diciembre de 2022;1(4):253-61. Disponible en: https://doi.org/10.1016/j.imj.2022.11.001

20. 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. noviembre de 2021;148(5):e2021052286. Disponible en: https://doi.org/10.1542/peds.2021-052286

21. Baird JK, Jensen SM, Urba WJ, Fox BA, Baird JR. SARS-CoV-2 Antibodies Detected in Mother’s Milk Post-Vaccination. J Hum Lact Off J Int Lact Consult Assoc. agosto de 2021;37(3):492-8. Disponible en: https://doi.org/10.1177/08903344211030168

22. 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. 21 de abril de 2022;14(1):42. Disponible en: https://doi.org/10.1186/s13073-022-01043-9

23. Low JM, Gu Y, Ng MSF, Wang LW, Amin Z, Zhong Y, et al. Human Milk Antibodies after BNT162b2 Vaccination Exhibit Reduced Binding against SARS-CoV-2 Variants of Concern. Vaccines. 31 de enero de 2022;10(2):225. Disponible en: https://doi.org/10.3390/vaccines10020225

24. 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. 24 de febrero de 2022;11(3):286. Disponible en: https://doi.org/10.3390/pathogens11030286

25. Golan Y, Prahl M, Cassidy AG, Gay C, Wu AHB, 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;12:777103. Disponible en: https://doi.org/10.1101/2022.12.12.22283367

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. 1 de febrero de 2022;176(2):159-68. Disponible en: https://doi.org/10.1001/jamapediatrics.2021.4897

27. Pérez-Bernal M, Hernández C, Ibargollín R, Martínez M, Soria M, Delgado M, et al. Anti-SARS-CoV-2 Omicron BA.5 RBD antibody titers generated by the protein subunit vaccine Abdala in breast milk. Vacunas. julio de 2024; 25(3):331-39. Disponible en: https://doi.org/10.1016/j.vacun.2024.05.001

28. Lam JS, Mansour MK, Specht CA, Levitz SM. A model vaccine exploiting fungal mannosylation to increase antigen immunogenicity. J Immunol. 1 de diciembre de 2005;175(11):7496-503. Disponible en: https://doi.org/10.4049/jimmunol.175.11.7496

29. Liu H, Wilson IA. Protective neutralizing epitopes in SARS-CoV-2. Immunol Rev. septiembre de 2022;310(1):76-92. Disponible en: https://doi.org/10.1111/imr.13084

30. Lisowska E. The role of glycosylation in protein antigenic properties. Cell Mol Life Sci CMLS. marzo de 2002;59(3):445-55. Disponible en: https://doi.org/10.1007/s00018-002-8437-3

31. Bäuerl C, Zulaica J, Rusu L, Moreno AR, Pérez-Cano FJ, Lerin C, et al. Assessment of SARS-CoV-2 neutralizing antibody titers in breastmilk from convalescent and vaccinated mothers. iScience. 4 de mayo de 2023;26(6):106802. Disponible en: https://doi.org/10.1016/j.isci.2023.106802

32. Omicron, Delta, Alpha, and More: What to Know About the Coronavirus Variants News Yale Medicine [Internet]. [citado 14 nov 2023]. Disponible en: https://www.yalemedicine.org/news/covid-19-variants-of-concern-omicron

33. Valcarce V, Stafford LS, Neu J, Cacho N, Parker L, Mueller M, et al. Detection of SARS-CoV-2-Specific IgA in the Human Milk of COVID-19 Vaccinated Lactating Health Care Workers. Breastfeed Med Off J Acad Breastfeed Med. diciembre de 2021;16(12):1004-9. Disponible en: https://doi.org/10.1101/2021.04.02.21254642

34. Kelly JC, Carter EB, Raghuraman N, Nolan LS, Gong Q, Lewis AN, et al. Anti-severe acute respiratory syndrome coronavirus 2 antibodies induced in breast milk after Pfizer-BioNTech/BNT162b2 vaccination. Am J Obstet Gynecol. julio de 2021;225(1):101-3. Disponible en: https://doi.org/10.1016/j.ajog.2021.03.031

35. 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. 16 de enero de 2022;10(1):125. Disponible en: https://doi.org/10.3390/vaccines10010125

36. Yin W, Xu Y, Xu P, Cao X, Wu C, Gu C, et al. Structures of the Omicron spike trimer with ACE2 and an anti-Omicron antibody. Science. 4 de marzo de 2022;375(6584):1048-53. Disponible en: https://doi.org/10.1126/science.abn8863

37. Liu H, Aviszus K, Zelarney P, Liao SY, Gerber AN, Make B, et al. Vaccine-elicited B- and T-cell immunity to SARS-CoV-2 is impaired in chronic lung disease patients. ERJ Open Res. 1 de septiembre de 2023;9(5). Disponible en: https://doi.org/10.1101/2023.01.25.23284971

38. Soegiarto G, Wulandari L, Purnomosari D, Dhia Fahmita K, Ikhwan Gautama H, Tri Hadmoko S, et al. Hypertension is associated with antibody response and breakthrough infection in health care workers following vaccination with inactivated SARS-CoV-2. Vaccine. 26 de junio de 2022;40(30):4046-56. Disponible en: https://doi.org/10.1016/j.vaccine.2022.05.059

39. Thomas AL, Alarcon PC, Divanovic S, Chougnet CA, Hildeman DA, Moreno-Fernandez ME. Implications of Inflammatory States on Dysfunctional Immune Responses in Aging and Obesity. Front Aging. 2021;2:732414. Disponible en: https://doi.org/10.3389/fragi.2021.732414

Published

2026-06-01

How to Cite

Pérez Bernal, M., Hernández Díaz, C., Ibargollín Ulloa, R., Martínez Barrios, M., Soria Díaz, M., Delgado Rigo, M., … Sánchez Ríos, J. M. (2026). SARS-CoV-2 anti-RBD immune response in breast milk from puerperal women vaccinated with Abdala. Anales De La Academia De Ciencias De Cuba, 16, e3265. Retrieved from https://revistaccuba.sld.cu/index.php/revacc/article/view/3265

Issue

Section

Biomedical sciences