RESUMEN
It has been shown that cytokines can act as molecular adjuvant to enhance the immune response induced by DNA vaccines, but it is unknown whether interleukin 33 (IL-33) can enhance the immunocontraceptive effect induced by DNA vaccines. In the present study, we explored the effects of murine IL-33 on infertility induced by Lagurus lagurus zona pellucida 3 (Lzp3) contraceptive DNA vaccine administered by the mucosal route. Plasmid pcD-Lzp3 and plasmid pcD-mIL-33 were encapsulated with chitosan to generate the nanoparticle chi-(pcD-Lzp3+pcD-mIL-33) as the DNA vaccine. Sixty female ICR mice, divided into 5 groups (n=12/group), were intranasally immunized on days 0, 14, 28, and 42. After intranasal immunization, the anti-LZP3-specific IgG in serum and IgA in vaginal secretions and feces were determined by ELISA. The results showed that chi-(pcD-Lzp3+pcD-mIL-33) co-immunization induced the highest levels of serum IgG, secreted mucosal IgA, and T cell proliferation. Importantly, mice co-immunized with chi-(pcD-Lzp3+pcD-mIL-33) had the lowest birth rate and mean litter size, which correlated with high levels of antibodies. Ovaries from infertile female mice co-immunized with chi-(pcD-Lzp3+pcD-mIL-33) showed abnormal development of ovarian follicles, indicated by atretic follicles and loss of oocytes. Our results demonstrated that intranasal delivery of the molecular adjuvant mIL-33 with chi-pcD-Lzp3 significantly increased infertility by enhancing both systemic and mucosal immune responses. Therefore, chi-(pcD-Lzp3+pcD-mIL-33) co-immunization could be a strategy for controlling the population of wild animal pests.
RESUMEN
Conservative sperm acrosomal antigens that react with a monoclonal sperm antibody against human spermatozoa HS63 were purified by immunoaffinity chromatography from rabbit testes. The purity and the molecular weight of the purified antigens were determined by SDS acrylamide gel electrophoresis. There is only a band on the acrylamide gel. The molecular weight is more than 60000. It is found that the antigen is a glycoprotein with the carbohydrate moiety of 17%. Following successive immunization antisera of high titers were raised and shown to react specifically with antigens on sperm acrosome, but not with any somatic cells as judged. By using mouse in vitro fertilization experiments and sperm penetration assay with zona-free hamster ova, the isoimmune sera from rabbit exhibited high degrees of fertilization inhibition as compared to the control sera. The results suggest that sperm-specific antigen reactive to HS63 may be a good candidates for the development of immunocontraceptive vaccines in humans.