Induction of early and bioeffective antibody response in rodents with the 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 with the luteinizing hormone-releasing hormone (LHRH) vaccine on prostatic hypertrophy and hyperplasia. A drawback of this vaccine was a delay of about 8 weeks in buildup of antibody titers to efficacy level and the requirement of three injections of the vaccine given at monthly interval for full primary immunization.


METHODS
LHRH vaccine was encapsulated in poly-lactic-co-glycolic acid (PLGA) 50:50 copolymer microspheres of reproducible physicochemical characteristics. Immunogenicity studies were carried out in rodents and prostate weights were determined at various antibody titers.


RESULTS
The vaccine entrapped in biodegradable microspheres generated high antibody response in rats, persisting for 5-7 months following a single immunization. One hundred micrograms was the optimum dose, and the intramuscular route was more immunogenic than the subcutaneous. It was further observed that coadministration of 75% of the vaccine entrapped in microspheres with 25% adsorbed on alum generated higher antibody response in rodents, exceeding the bioeffective threshold as early as day 15 postimmunization.


CONCLUSIONS
Coadministration of the LHRH vaccine in biodegradable PLGA microspheres with a quarter of the dose adsorbed on alum generates high antibody titers within 15 days, which are effective in causing atrophy of the prostate.
Diwan
M
M
Department of Reproductive Health and Vaccinology, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India.
Dawar
H
H
Talwar
G P
GP
D000534:Alum Compounds; D000818:Animals; D000917:Antibody Formation; D001673:Biodegradation, Environmental; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000276:immunology* / Q000493:pharmacokinetics; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008863:Microspheres; D011467:Prostate / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000628:therapy; D051381:Rats; D017208:Rats, Wistar; D014612:Vaccines
D000534:Alum Compounds; D014612:Vaccines; D007987:Gonadotropin-Releasing Hormone; C041524:aluminum sulfate