Immunogenicity and contraceptive potential of a human zona pellucida 3 peptide vaccine

Harini Bagavant, Francesco M. Fusi, Jeanine Baisch, Barbara Kurth, Chella S. David, Kenneth S K Tung

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Immunization with zona pellucida 3 (ZP3) glycoprotein induces infertility in primates and is a target antigen for a contraceptive vaccine. However, loss of ovarian function is a long-term side effect. A possible mechanism is autoimmune ovarian disease induced by ZP3-specific autoreactive T cells, demonstrated in mice immunized with a murine ZP3 peptide in complete Freund's adjuvant. Indeed, a murine contraceptive vaccine that elicits antibodies to zona pellucida (ZP) without concomitant pathogenic T-cell activation has been achieved by a chimeric peptide (CP) consisting of a native ZP3 B-cell epitope and a foreign helper T-cell peptide. Herein, we evaluate the CP strategy in primate for human ZP3 (hZP3) vaccine development. A CP was constructed that consisted of a known helper T-cell epitope from the malarial circumsporozoite protein and a native B-cell epitope of hZP3. The human CP elicited antibodies to ZP3 in macaques without a measurable T-cell response to the hZP3 peptide. The serum antibodies reacted with macaque and human ZP and significantly inhibited human sperm binding to oocytes in vitro. Moreover, the CP elicited antibodies to human ZP in mice that lack murine major histocompatibility complex (MHC) class II molecules but express transgenic human HLA-DR3, -DQ6, or -DQ8 molecules. Therefore, this study 1) provides evidence to support the feasibility of the CP strategy in hZP3 vaccine development and 2) describes a novel approach for evaluating the influence of polymorphic human MHC on vaccine immunogenicity without human immunization.

Original languageEnglish (US)
Pages (from-to)764-770
Number of pages7
JournalBiology of Reproduction
Volume56
Issue number3
DOIs
StatePublished - Mar 1997

Fingerprint

Zona Pellucida
Subunit Vaccines
Contraceptive Agents
Peptides
Contraceptive Vaccines
B-Lymphocyte Epitopes
Antibodies
Macaca
Helper-Inducer T-Lymphocytes
Major Histocompatibility Complex
T-Lymphocytes
Primates
Immunization
Vaccines
HLA-DR3 Antigen
Ovarian Diseases
T-Lymphocyte Epitopes
Freund's Adjuvant
Infertility
Autoimmune Diseases

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Embryology

Cite this

Bagavant, H., Fusi, F. M., Baisch, J., Kurth, B., David, C. S., & Tung, K. S. K. (1997). Immunogenicity and contraceptive potential of a human zona pellucida 3 peptide vaccine. Biology of Reproduction, 56(3), 764-770. https://doi.org/10.1095/biolreprod56.3.764

Immunogenicity and contraceptive potential of a human zona pellucida 3 peptide vaccine. / Bagavant, Harini; Fusi, Francesco M.; Baisch, Jeanine; Kurth, Barbara; David, Chella S.; Tung, Kenneth S K.

In: Biology of Reproduction, Vol. 56, No. 3, 03.1997, p. 764-770.

Research output: Contribution to journalArticle

Bagavant, H, Fusi, FM, Baisch, J, Kurth, B, David, CS & Tung, KSK 1997, 'Immunogenicity and contraceptive potential of a human zona pellucida 3 peptide vaccine', Biology of Reproduction, vol. 56, no. 3, pp. 764-770. https://doi.org/10.1095/biolreprod56.3.764
Bagavant, Harini ; Fusi, Francesco M. ; Baisch, Jeanine ; Kurth, Barbara ; David, Chella S. ; Tung, Kenneth S K. / Immunogenicity and contraceptive potential of a human zona pellucida 3 peptide vaccine. In: Biology of Reproduction. 1997 ; Vol. 56, No. 3. pp. 764-770.
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