Development of a hormone neutralizing vaccine, using GnRH-glycys-PPD, for use in the treatment of oestrogen-dependent disorders.
The aim of this study was to develop an effective and nontoxic vaccine, suitable for use in humans, which was capable of effectively controlling oestrogen levels. Female Sprague-Dawley rats were immunized with a conjugated analogue of gonadotrophin releasing hormone, GnRH-glycys-PPD. This resulted in high levels of neutralizing antibody which disrupted GnRH function and consequently caused a reduction in serum oestrogen. The effect of oestrogen deprivation correlated well with ovarian failure and gonadal atrophy. An examination was made of various adjuvants in conjunction with the analogue to determine the suitability of the combinations in the formulation of an effective human vaccine. This investigation included a novel adjuvant, non-ionic surfactant vesicles (NISV); the results showed that NISV are completely nontoxic and in terms of potentiating and sustaining an immune response, compare favourably with Freund's adjuvant and alum. In addition the long term effects of immunization were investigated and the data showed that immunoneutralization of GnRH effectively suppresses fertility on a long-term basis.
Ferro
V A
VA
University of Strathclyde, Department of Immunology, Glasgow, UK.
O'Grady
J E
JE
Notman
J
J
Stimson
W H
WH
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000906:Antibodies / Q000097:blood; D001835:Body Weight; D004958:Estradiol / Q000097:blood; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000276:immunology*; D007114:Immunization; D007247:Infertility, Female / Q000209:etiology*; D009929:Organ Size; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000187:drug effects / Q000473:pathology; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014621:Vagina / Q000187:drug effects / Q000473:pathology
D000276:Adjuvants, Immunologic; D000906:Antibodies; D004965:Estrogen Antagonists; D014612:Vaccines; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol