Immunogenicity of a multi-component recombinant human acrosomal protein vaccine in female Macaca fascicularis

Abstract

A vaccine formula comprised of five recombinant human intra-acrosomal sperm proteins was innoculated into female monkeys to test whether specific antibodies to each component immunogen could be elicited in sera and whether antibodies elicited by the vaccine affected in vitro fertilization. Acrosomal proteins, ESP, SLLP-1, SAMP 32, SP-10 and SAMP 14, were expressed with his-tags, purified by nickel affinity chromatography and adsorbed to aluminum hydroxide. Five female cynomolgus monkeys were inoculated intramuscularly 3 times at monthly intervals. All five monkeys developed both IgG and IgA serum responses to each recombinant immunogen on Western blots. Each serum stained the acrosome of human sperm and bound to the cognate native protein on Western blots of human sperm extracts. By ELISA, all monkeys developed IgG to each immunogen, with the highest average absorbance values to ESP, SAMP 32 and SP-10, followed by lower values for SLLP-1 and SAMP 14. IgA was also generated to each component immunogen with the highest average absorbance values to SLLP-1 and SP-10. For antigens that induced an IgA response, the duration of the IgA response was longer than the IgG response to the same antigens. This study supports the concept that a multivalent contraceptive vaccine may be administered to female primates evoking both peripheral (IgG) and mucosal (IgA) responses to each component immunogen following an intramuscular route of inoculation with a mild adjuvant, aluminum hydroxide, approved for human use.

Identification of novel immunodominant epididymal sperm proteins using combinatorial approach

“…In order to achieve 100% contraceptive effect, the proteins on different domains of sperm need to be targeted, as every domain is responsible for a function leading to successful fertilization. It has been suggested that immunization with a multivalent vaccine containing multiple sperm antigens can generate a greater anti-fertility effect than a single sperm antigen (Kurth et al 2008). As part of our effort to identify putative protein targets for the development of posttesticular male contraceptives, we exploited combinatorial approach of SI followed by proteomics to delineate potential targets from different sperm domains.…”

“…For a target to be considered suitable for a vaccine approach, immunogenicity is very crucial and therefore separate studies have been specially designed by investigators to establish immunogenicity of otherwise well-characterized proteins such as ESP, SLIP-1, SPACA1, ACRV1, and SPACA4 (Kurth et al 2008. Our approach was unique as it identified only those proteins, which are immunogenic, ruling out the need for a separate study to establish the immunogenicity of the identified proteins.…”

Preparation, Characterization, and Determination of Immunological Activities of Transfer Factor Specific to Human Sperm Antigen

“…Various health organizations and pharmaceutical companies actively continue to pursue research towards new contraceptive approaches [2]. Presently, based on the variable antigens (Ags) existing in the male reproductive system, researchers have developed many antibodies (Abs) or vaccines for contraception, such as Abs to SP-10 expressed in the testis that could interfere with the union of sperm and ovum [3]. The sperm-specific protein, Izumo, a member of immunoglobulin superfamily (IgSF) which is located on the sperm stimulates hamster to secrete high titer of Abs both in the genital tract and serum and further decreases their reproductive capability [4].…”

Evaluation of Contraceptive Potential of a Novel Epididymal Sperm Protein SFP2 in a Mouse Model

“…The idea to use sperm proteins as contraceptives arose from studies reporting infertility in 70% of the vasectomized men and 30% of the infertile couple due of the presence antisperm antibodies. 11,12 With the objective to identify more targets, we recently reported several novel epididymis-specific proteins using the combinatorial approach. 5 Decline of fertility post-immunization with sperm proteins has been reported.…”