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

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41 Scopus citations

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 1 1997

ASJC Scopus subject areas

  • Cell Biology

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    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