Contraceptive vaccine assessment based on a murine ZP3 mini-autoantigen

Abstract

A summary is presented of published and some unpublished observations from studies on the immunological response of mice to a 13-mer peptide of the murine ovarian zona pellucida glycoprotein ZP3. The findings have the following implications for the design of immunocontraceptive vaccines. To be reversible, a ZP3 vaccine must not contain pathogenic T cell epitopes of ZP3, but contraception without autoimmune oophoritis may be feasible. The immune response to the ZP3 mini-autoantigen is highly variable among inbred mouse strains, suggesting that a single oophoritogenic peptide would not achieve irreversible contraception in an outbred population. The discovery of antigen mimicry at the level of T cell peptide has thrown doubt on the validity of current strategy in detecting relevant self-antigens that might cross react with vaccine immunogens and on the feasibility of fully predicting the cross-reactive autoimmunogenic potential of a peptide or polypeptide vaccine antigen. Autoantibodies directed against epitopes outside the ZP3 mini-autoantigen, produced by immunization with the pure T cell epitope, react with high affinity, with native zona pellucida, and may be useful in identifying B cell epitopes in ZP3.

Antibody Responses and Infertility in Mice Following Oral Immunization with Attenuated Salmonella typhimurium Expressing Recombinant Murine ZP31

“…Simultaneously, it may also lead to activation of ZP3-specific T cells that in turn could cause autoimmune ovarian disease. It has been demonstrated that T cells per se (probably Thl phenotype), not autoantibody, initiate the disease in a mouse model [27,32]. For a contraceptive vaccine using a conventional immunization strategy, it will be extremely important to avoid inclusion of the harmful T-cell epitope with the useful ZP3 B-cell epitope [15].…”

Cloning and characterisation of a zona pellucida 3 cDNA from a marsupial, the brushtail possum Trichosurus vulpecula

“…Further studies are required to determine whether C-terminal processing occurs in the possum and to examine the function of this non-conserved region in marsupial fertilisation. Peptide vaccines based on this epitope have been investigated in mice and primates (Tung et al, 1994;Bagavant et al, 1997) and are currently being examined for their ability to elicit an immune response and block fertilisation in the brushtail possum. Figure 5 Analysis of ZP3 expression in tissues of adult brushtail possum (Trichosurus vulpecula).…”

Viewpoint: Measuring the effects of wildlife contraception: the argument for comparing apples with oranges

“…Immunocontraceptives, regardless of their physiological targets, most commonly the zona pellucida of the ovum (Tung et al 1994;Kaul et al 1996) or the gonadotropin-releasing hormone of the hypothalamus (GnRH; Hunter and Byers 1996), and contraceptives delivered in biologically modified organisms (Robinson et al 1997) present another potential genetic concern. Because the immunocompetence of differing species (Frank et al 2005), differing strains (Haddad et al 1994) and even individual animals in a single population (Lyda et al 2005) is often markedly different, immunocontraception has the potential to skew population genetics.…”