Immunogenicity and contraceptive efficacy of recombinant fusion protein encompassing Sp17 spermatozoa-specific protein and GnRH: Relevance of adjuvants and microparticles based delivery to minimize number of injections.

Problem: Requirement of multiple injections of contraceptive vaccines to achieve infertility is one of the important impediments for their application. In the present study, attempts have been made to reduce the number of injections of contraceptive vaccine.
Method of Study: Fusion protein encompassing C-terminus fragment of sperm protein Sp17 (aa residues 76-126) and two copies of gonadotropin-releasing hormone along with T-cell epitopes and dilysine linkers (abbreviated as Sp17 _C -GnRH ₂ ) was expressed in Escherichia coli. Its immunogenicity and contraceptive efficacy have been evaluated in female FVB/J mice using different adjuvants and delivery platforms.
Results: Immunization of female mice with recombinant Sp17 _C -GnRH ₂ (25 μg/injection/mouse) emulsified with squalene-arlacel A following two injections schedule led to failure of 88.8% immunized animals to conceive, which was not significantly different from mice immunized with same protein along with alum following three injections schedule. To make single-dose vaccine, poly d,l-lactic acid-based microparticles (PLA-MPs) entrapping Sp17 _C -GnRH ₂ were prepared. Immunization of female mice with a combination of soluble Sp17 _C -GnRH ₂ (12.5 μg/injection/mouse) along with Sp17 _C -GnRH ₂ entrapped in PLA-MPs (12.5 μg/injection/mouse) in alum showed higher antibody titres and contraceptive efficacy as compared to mice immunized with Sp17 _C -GnRH ₂ entrapped in PLA-MPs alone in alum. Immunization with recombinant Sp17 _C -GnRH ₂ led to long-term infertility as second mating (150 days after immunization) of various groups of immunized mice showed similar infertility as observed during first mating.
Conclusion: Single-dose immunization with PLA-MPs entrapping Sp17 _C -GnRH ₂ along with soluble recombinant protein in alum generated long-lasting infertility in female mice.
(© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)