A dual kisspeptin-GnRH immunogen for reproductive immunosterilization

Abstract

GnRH immunogens have been extensively employed in immunocontraception of animals. While they are effective, they are not 100% efficacious and of limited duration. GnRH secretion is dependent on upstream stimulation by kisspeptin. We therefore hypothesised that a dual immunogen combining GnRH and kisspeptin may be more efficacious through targeting two levels of the axis. We have previously shown GnRH immunogen elicits permanent sterilisation when sheep are vaccinated neonatally suggesting that the efficacy of GnRH immunisation may be dependent on the stage of reproductive development. We have now studied over 300 days the efficacy of immunisation with a dual immunogen comprising GnRH linked to kisspeptin via a hepatitis B T helper peptide sequence (GKT) administered to male and female rats prepubertally, pubertally and as adults. At all stages of development all immunised animals produced antibodies to GnRH, kisspeptin and GKT but differentially in titre with respect to sex and stage of development. In immunised adult, prepubertal and pubertal males testosterone and testes length was markedly reduced by 60 days and remained at low levels until day 150. Thereafter, testosterone recovered to pre immunisation levels and testes length increased to a maximum of about 40% of controls. 80% of males were infertile in three matings over 250 days. In prepubertal and pubertal female rats a single immunisation at day 0 reduced estradiol to low levels by day 60 which remained low until termination of the experiment on day 300. In matings of these females with fertile males on days 90, 120 and 250, 74% of prepubertal females were infertile and impressively, 100% (10/10) of pubertal females were infertile after a single immunisation on day 0. These findings set the scene for exploration of immunosterilisation of wild and domestic animals after a single immunisation.