Insights into the Regulatory Mechanism Controlling the Inhibition of Vaccine-induced Seroconversion by Maternal Antibodies

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2011 Mar 2

PMID 21357766

Citations 41

Authors

Dhohyung Kim

Devra Huey

Michael Oglesbee

Stefan Niewiesk

Affiliations

Soon will be listed here.

Abstract

The inhibition of vaccination by maternal antibodies is a widely observed phenomenon in human and veterinary medicine. Maternal antibodies are known to suppress the B-cell response. This is similar to antibody feedback mechanism studies where passively transferred antibody inhibits the B-cell response against particulate antigens because of epitope masking. In the absence of experimental data addressing the mechanism underlying inhibition by maternal antibodies, it has been suggested that epitope masking explains the inhibition by maternal antibodies, too. Here we report that in the cotton rat model of measles virus (MV) vaccination passively transferred MV-specific immunoglobulin G inhibit B-cell responses through cross-linking of the B-cell receptor with FcγRIIB. The extent of inhibition increases with the number of antibodies engaging FcγRIIB and depends on the Fc region of antibody and its isotype. This inhibition can be partially overcome by injection of MV-specific monoclonal IgM antibody. IgM stimulates the B-cell directly through cross-linking the B-cell receptor via complement protein 3d and antigen to the complement receptor 2 signaling complex. These data demonstrate that maternal antibodies inhibit B-cell responses by interaction with the inhibitory/regulatory FcγRIIB receptor and not through epitope masking.

Citing Articles

Dynamic Immune Response Landscapes of Avian Peripheral Blood Post-Vaccination Against Infectious Bronchitis Virus Infection.

Li X, Liang Y, Zhang Y, Liu Z, Cui L, Xi M Vaccines (Basel). 2025; 13(2).

PMID: 40006693 PMC: 11861738. DOI: 10.3390/vaccines13020146.

The Generation of a H9N2 Avian Influenza Virus with HA and C3d-P29 Protein Fusions and Vaccine Development Applications.

Pan X, Zhou F, Shi X, Liu Q, Yan D, Teng Q Vaccines (Basel). 2025; 13(2).

PMID: 40006646 PMC: 11861068. DOI: 10.3390/vaccines13020099.

Influenza virus antibodies inhibit antigen-specific B cell responses in mice.

Goodwin E, Gibbs J, Yewdell J, Eisenlohr L, Hensley S J Virol. 2024; 98(9):e0076624.

PMID: 39194245 PMC: 11406888. DOI: 10.1128/jvi.00766-24.

Evaluation of mRNA-LNP and adjuvanted protein SARS-CoV-2 vaccines in a maternal antibody mouse model.

England R, Drapeau E, Alameh M, Hosseinzadeh R, Weissman D, Hensley S NPJ Vaccines. 2024; 9(1):110.

PMID: 38890316 PMC: 11189435. DOI: 10.1038/s41541-024-00901-4.

Attenuation and molecular characterization of fowl adenovirus 8b propagated in a bioreactor and its immunogenicity, efficacy, and virus shedding in broiler chickens.

Ugwu C, Hair-Bejo M, Nurulfiza M, Omar A, Ideris A Vet World. 2024; 17(4):744-755.

PMID: 38798289 PMC: 11111708. DOI: 10.14202/vetworld.2024.744-755.

References

Getahun A, Heyman B . Studies on the mechanism by which antigen-specific IgG suppresses primary antibody responses: evidence for epitope masking and decreased localization of antigen in the spleen. Scand J Immunol. 2009; 70(3):277-87. DOI: 10.1111/j.1365-3083.2009.02298.x. View

Takai T, Ono M, Hikida M, Ohmori H, Ravetch J . Augmented humoral and anaphylactic responses in Fc gamma RII-deficient mice. Nature. 1996; 379(6563):346-9. DOI: 10.1038/379346a0. View

Englund J, Anderson E, Reed G, Decker M, Edwards K, Pichichero M . The effect of maternal antibody on the serologic response and the incidence of adverse reactions after primary immunization with acellular and whole-cell pertussis vaccines combined with diphtheria and tetanus toxoids. Pediatrics. 1995; 96(3 Pt 2):580-4. View

Martins C, Garly M, Bale C, Rodrigues A, Ravn H, Whittle H . Protective efficacy of standard Edmonston-Zagreb measles vaccination in infants aged 4.5 months: interim analysis of a randomised clinical trial. BMJ. 2008; 337:a661. PMC: 2500198. DOI: 10.1136/bmj.a661. View

Siegrist C . Mechanisms by which maternal antibodies influence infant vaccine responses: review of hypotheses and definition of main determinants. Vaccine. 2003; 21(24):3406-12. DOI: 10.1016/s0264-410x(03)00342-6. View

Gans H, DeHovitz R, Forghani B, Beeler J, Maldonado Y, Arvin A . Measles and mumps vaccination as a model to investigate the developing immune system: passive and active immunity during the first year of life. Vaccine. 2003; 21(24):3398-405. DOI: 10.1016/s0264-410x(03)00341-4. View

Klaus G . Differing effects of monoclonal anti-hapten antibodies on humoral responses to soluble or particulate antigens. Immunology. 1984; 52(1):129-36. PMC: 1454600. View

Sinclair N, Lees R, ELLIOTT E . Role of the Fc fragment in the regulation of the primary immune response. Nature. 1968; 220(5171):1048-9. DOI: 10.1038/2201048a0. View

Nakamura A, Yuasa T, Ujike A, Ono M, Nukiwa T, Ravetch J . Fcgamma receptor IIB-deficient mice develop Goodpasture's syndrome upon immunization with type IV collagen: a novel murine model for autoimmune glomerular basement membrane disease. J Exp Med. 2000; 191(5):899-906. PMC: 2195851. DOI: 10.1084/jem.191.5.899. View

10.

Johnson C, Darbari A, Darbari D, Nalin D, Whitwell J, Chui L . Measles vaccine immunogenicity and antibody persistence in 12 vs 15-month old infants. Vaccine. 2000; 18(22):2411-5. DOI: 10.1016/s0264-410x(99)00574-5. View

11.

DAmbrosio D, Hippen K, Minskoff S, Mellman I, Pani G, Siminovitch K . Recruitment and activation of PTP1C in negative regulation of antigen receptor signaling by Fc gamma RIIB1. Science. 1995; 268(5208):293-7. DOI: 10.1126/science.7716523. View

12.

Siegrist C, Barrios C, Martinez X, Brandt C, Berney M, COrdova M . Influence of maternal antibodies on vaccine responses: inhibition of antibody but not T cell responses allows successful early prime-boost strategies in mice. Eur J Immunol. 1998; 28(12):4138-48. DOI: 10.1002/(SICI)1521-4141(199812)28:12<4138::AID-IMMU4138>3.0.CO;2-L. View

13.

Heyman B . Regulation of antibody responses via antibodies, complement, and Fc receptors. Annu Rev Immunol. 2000; 18:709-37. DOI: 10.1146/annurev.immunol.18.1.709. View

14.

Graves M, Griffin D, Johnson R, Hirsch R, De Soriano I, ROEDENBECK S . Development of antibody to measles virus polypeptides during complicated and uncomplicated measles virus infections. J Virol. 1984; 49(2):409-12. PMC: 255480. DOI: 10.1128/JVI.49.2.409-412.1984. View

15.

C Willcocks L, Smith K, Clatworthy M . Low-affinity Fcgamma receptors, autoimmunity and infection. Expert Rev Mol Med. 2009; 11:e24. DOI: 10.1017/S1462399409001161. View

16.

TAO T, UHR J . Capacity of pepsin-digested antibody to inhibit antibody formation. Nature. 1966; 212(5058):208-9. DOI: 10.1038/212208a0. View

17.

Schlereth B, Buonocore L, Tietz A, Meulen V, Rose J, Niewiesk S . Successful mucosal immunization of cotton rats in the presence of measles virus-specific antibodies depends on degree of attenuation of vaccine vector and virus dose. J Gen Virol. 2003; 84(Pt 8):2145-2151. DOI: 10.1099/vir.0.19050-0. View

18.

Gans H, Maldonado Y, Yasukawa L, Beeler J, Audet S, Rinki M . IL-12, IFN-gamma, and T cell proliferation to measles in immunized infants. J Immunol. 1999; 162(9):5569-75. View

19.

Wiersma E, Coulie P, Heyman B . Dual immunoregulatory effects of monoclonal IgG-antibodies: suppression and enhancement of the antibody response. Scand J Immunol. 1989; 29(4):439-48. DOI: 10.1111/j.1365-3083.1989.tb01143.x. View

20.

Schlereth B, Rose J, Buonocore L, Ter Meulen V, Niewiesk S . Successful vaccine-induced seroconversion by single-dose immunization in the presence of measles virus-specific maternal antibodies. J Virol. 2000; 74(10):4652-7. PMC: 111985. DOI: 10.1128/jvi.74.10.4652-4657.2000. View