Immunocastration with gene vaccine (KISS1) induces a cell‐mediated immune response in ram testis: A transcriptome evaluation

Abstract

Immunocastration vaccines achieve their effects through neutralization of the endogenous hormone by the humoral antibody produced against the immunized genes, but there is little information regarding cell‐mediated immune response on the gonadal function of the immunized model is available. In this study, we used ram as a model animal to identify the cellular immune response in testicular tissues of rams immunized with intranasal KISS1 gene vaccine. The immune castration model was evaluated by sexual behaviours, spermatogenesis and serum hormone profiles after the KISS1 gene immunization. Transcriptome analysis of testicular tissues was carried out to identify the expressions of protein‐coding genes involved in cellular immunity. The results showed that we successfully constructed the KISS1 immune castration ram model, in which testicular growth and development, testosterone and kisspeptin‐54 levels, and sexual function were suppressed in immunized rams (p < .05). Using Hiseq™ 2000 high sequencing for ram testicular, we identified 21 differentially expressed genes (DEGs) related to cellular immunity, of which, 14 genes were upregulated and seven genes were downregulated in the testis of the immunized group (p < .05). The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment showed that these differentially expressed genes were enriched in the antigen presentation process mediated by MHC class I and the cytotoxic pathway mediated by natural killer cells. It is concluded that KISS1 gene vaccine induced the cell‐mediated immune response in testicular tissue to suppress reproductive activities in rams.

Male animal sterilization: history, current practices, and potential methods for replacing castration

“…Although the vaccine showed promise for inhibiting male fertility in the ram, the effect was not permanent, as testosterone production and spermatogenesis recovered by weeks 22 to 30 post-immunization ( 537 ). Another study in rams immunized with pKS-asd reported a significant alteration in the expressions of genes associated with cellular immunity specific to the testis ( 469 ). Specific effects were noted on the cytotoxic pathway of Leydig cells mediated by natural killer cells, and it was suggested that these could lead to permanent infertility.…”

“…In the US, the technology for antibody-mediated immunocontraception received a patent in 2014 ( 467 ). Although most immune methods that only provide contraception and reimmunizations are necessary, studies have shown that sterility can be achieved by using specific methods and immune targets ( 195 , 468 , 469 ).…”

“…Other outcomes in small ruminants indicate that KISS1-mediated immunocastration would be an interesting alternative for castration of farm animals. First, both PBK-asd and pKS-asd immunization decreased aggression and sexual behaviors in rams (i.e., frequency of mounting, sniffing, and butting) ( 469 , 536 ). Second, bucks immunized with PBK-asd showed similar growth and carcass and meat characteristics compared with intact bucks, whereas surgical castration reduced daily gain and carcass weight ( 539 ).…”

The protective role of maternal genetic immunization on maternal‐fetal health and welfare

“…vaccines are often safer than other vaccines because they carry only antigen genetic information, are more stable and easier to produce, and can stimulate both humoral and cellular immune responses. 24,38,39 Intrinsic elements of gene vaccine can also activate innate immune responses, thereby enhancing adaptive immune responses against the expressed antigens. Immunization with plasmid DNA antigen provides long-term tissue expression compared with protein antigens, and is potentially able to prime a strong immune response.…”

“…Genetic vaccines contain genetic material such as mRNA or DNA plasmids encoded with one or multiple genes, which are engaged by host defense cells and translated into protein. Genetic vaccines are often safer than other vaccines because they carry only antigen genetic information, are more stable and easier to produce, and can stimulate both humoral and cellular immune responses 24,38,39 . Intrinsic elements of gene vaccine can also activate innate immune responses, thereby enhancing adaptive immune responses against the expressed antigens.…”