Immunological cross-reactivity of antibodies with species chorionic gonadotropin is a critical requirement for efficacy testing of human gonadotropin vaccines in sub-human primates

Abstract

A key question in the evaluation of a contraceptive vaccine is its efficacy in the prevention of pregnancy. Primates have been employed for evaluation of the efficacy of candidate vaccines against human chorionic gonadotropin (hCG). Discrepancies have been noted between the immuno-reactive antibody titres (against hCG) determined by RIA and their ability to prevent pregnancy in test animals. To gain further information on factors involved in fertility control, other characteristics of antibodies, such as affinity for hCG, bioneutralization capacities for hCG, hLH and monkey chorionic gonadotropin, have been determined in antisera from ten bonnet monkeys (Macaca radiata) at times when they were infertile and in bleeds preceding conception. The data reported show that the most important correlate for efficacy is the bioneutralization capacity of the antibodies for the species CG; animals became pregnant when the neutralization capacity diminished to low levels (<45 IU/1≡5 ng/ml of hCG equivalent). The bioneutralization of heterospecies CG decreased with the increase in affinity for hCG. These findings have implications for the choice and suitability of primate species for the various candidate vaccines being developed. Vaccines inducing highly specific antibodies against hCG, and restricted in their reactivity with primate CG, may not be testable in heterospecies primate models.