Mouse-specific immunocontraceptive
peptides have been identified in mouse
proteins with key roles in reproduction from sequence comparisons to other species and tested for efficacy as immunocontraceptive
antigens.
Peptides were derived from
granulocyte-macrophage colony-stimulating factor (GMCSF), the placental 27 kDa
heat-shock protein (HSP),
leukemia inhibitory factor receptor (LIFR), oviduct
glycoprotein (OGP), proliferin (PLF),
prolactin (PRL), sperm
protein SP56 and mouse zona pellucida subunits 1 and 3 (ZP1, ZP3). Fertility of female BALB/c mice was reduced after immunization with several
peptides either conjugated to a
carrier protein or in the form of recombinant polyepitopes. The most effective conjugated
peptides (SP56, GMCSF and PRL) induced
peptide-specific serum
antibodies and reduced fertility by 50%. Fertility of mice was also reduced after immunization with polyepitope
antigens containing up to five different
peptides fused to
maltose-binding protein, but
antibodies were not produced against all the encoded
peptides. The most effective polyepitope
antigen (containing PLF, SP56, ZP1 and ZP3
peptides) reduced fertility by 50% but induced only SP56 and ZP1
antibodies. We demonstrate that lack of antibody response to a given
peptide epitope (ZP3) can be overcome if repeated copies are used in the polyepitope
antigen construct, but the effect varies between mouse strains. We conclude that
infertility induced in mice with a range of
peptide-based
vaccines is dependent on
antigen formulation and genetic factors but does not necessarily correlate with
peptide-specific antibody levels. In light of these results, strategies to improve the efficacy of
peptide-based
antifertility vaccines are discussed.