Role of adjuvants in the efficacy of an IZUMO1-based immunocontraceptive vaccine in mice

The binding of the sperm protein IZUMO1 to the oocyte receptor JUNO is an essential step in fertilization. Genetic deletion of IZUMO1 results in sterility, making this sperm protein a potential target for the development of an immunocontraceptive vaccine for the control of wildlife populations. However, contradictory results of the effect of immunization with IZUMO1 or IZUMO1-derived peptides have been reported. In this study, the effect of immunization with a recombinant mouse IZUMO1 peptide comprised of the extracellular Izumo, hairpin and Ig-like domains of IZUMO1 with different adjuvants was investigated in mice. The adjuvants were AddaS03, the nanoparticle adjuvant NanoST, composed of α-D-glucan nanoparticles and the STING agonist ADU-S100, or a combination of these two adjuvants. Immunization of outbred female mice induced a robust anti-IZUMO1 IgG response with significantly higher serum IgG2a titers in mice immunized with NanoST compared with AddaS03. Vaccines with NanoST alone or in combination with AddaS03 reduced the pregnancy rate and number of pups by more than 50 %, whereas vaccines formulated with AddaS03 alone had a limited effect. Infertility correlated with IgG directed against epitopes in the hairpin region of IZUMO1. These results support the further development of IZUMO1-based immunocontraceptive vaccines for wildlife population control.