INDUCTION OF EARLY AND BIOEFFECTIVE ANTIBODY-RESPONSE IN RODENTS WITHTHE LUTEINIZING-HORMONE-RELEASING HORMONE VACCINE GIVEN AS A SINGLE-DOSE IN BIODEGRADABLE MICROSPHERES ALONG WITH ALUM

BACKGROUND. Previous studies in animals and phase I/phase II clinical trials in humans have shown the suppressive effect of immunization wit h the luteinizing hormone-releasing hormone (LHRH) vaccine on prostati c hypertrophy and hyperplasia. A drawback of this vaccine was a delay of about 8 weeks in buildup of antibody titers to efficacy level and t he requirement of three injections of the vaccine given at monthly int erval for full primary immunization. METHODS. LHRH vaccine was encapsu lated in poly-lactic-co-glycolic acid (PLGA) 50:50 copolymer microsphe res of reproducible physicochemical characteristics. Immunogenicity st udies were carried out in rodents and prostate weights were determined at various antibody titers. RESULTS. The vaccine entrapped in biodegr adable microspheres generated high antibody response in rats, persisti ng for 5-7 months following a single immunization. One hundred microgr ams was the optimum dose, and the intramuscular route was more immunog enic than the subcutaneous. It was further observed that coadministrat ion of 75% of the vaccine entrapped in microspheres with 25% adsorbed on alum generated higher antibody response in rodents, exceeding the b ioeffective threshold as early as day 15 postimmunization. CONCLUSIONS . Coadministration of the LHRH vaccine in biodegradable PLGA microsphe res with a quarter of the dose adsorbed on alum generates high antibod y titers within 15 days, which are effective in causing atrophy of the prostate. (C) 1998 Wiley-Liss, Inc.