Development of male contraceptive vaccine - a perspective

This paper reviews the recent advances that have occurred inthe area of development of a male contraceptive vaccine. Thevaccine candidates considered for review are hormone/hormonereceptor-based proteins including luteinizing hormone-releasinghormone (LHRH)/LH, follicle stimulating hormone (FSH), as wellas LH and FSH receptor proteins. The review also highlight theadvances in our basic understanding of gonadotrophin actionwhich have led to development of these vaccines. Focus is mainlyon studies in the non-human primate which may be directly relevantto projected studies in the human. The data indicate that thevaccines are well tolerated by the primate (including the humanbased on limited data) and do not give rise to any known toxicsymptoms or immediate health hazards. The response to the immunogenhas been uniform and it may be possible to increase antibodytitres as well as prolong the immune response by adding acceptableimmune stimulators to the adjuvant cocktail and developing betterimmunization schedules or immunogen delivery systems. Contraceptivevaccines for the male are a feasible proposition and attentionshould now be focussed on evaluating carefully the bioefficacyof antibodies raised to recombinant ovine FSHß orFSH receptor protein fragments in both human and non-human primates.The advantage of the FSH/FSH receptor over the LHRH/LH-basedvaccine lies in the fact that the former does not require anexogenous testosterone supplement to maintain accessory glandfunction, libido etc. The LHRH/LH-based vaccine results in azoospermia,while the FSH vaccine causes the production of low numbers ofpoor quality spermatozoa which are incapable of impregnatingcycling females.     

Loss of suppression of normal bone marrow colony formation by leukemic cell lines after differentiation is induced by chemical agents

The human leukemic cell lines K562 and HL-60 were cocultured with normal bone marrow (BM) cells. Coculture with 10(4) K562 or HL-60 cells results in 50% inhibition of normal CFU-E and BFU-E colony formation. However, when the same number of K562 and HL-60 cells is first treated for two to five days with agents that induce their differentiation, a gradual loss in their capacity to inhibit CFU-E and BFU-E colony formation is observed. The inhibitory material in K562 cells is soluble and present in conditioned medium from cultures of these cells. The degree to which leukemic cell suppression of CFU-E and BFU-E growth is reversed is correlated with the time of exposure to the inducing agent. Suppression is no longer evident after five days of prior treatment with inducers. In fact, up to a 90% stimulation of CFU-E growth is observed in cocultures with K562 cells that have been pretreated with 30 to 70 mumol/L hemin for five days. K562 cells treated with concentrations of hemin as low as 30 mumol/L demonstrate increased hemoglobin synthesis and grow normally, but no longer have an inhibitory effect on CFU-E growth. Hence, reversal of normal BM growth inhibition must be caused by the more differentiated state of the K562 cells and not by a decrease in the number of these cells with treatment. Thus, induction of differentiation in cultured leukemic cells not only alters the malignant cell phenotype but also permits improved growth of accompanying normal marrow progenitor cells. Both are desired effects of chemotherapy.