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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
Author(s) -
Diwan Manish,
Dawar Hema,
Talwar G.P.
Publication year - 1998
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(19980601)35:4<279::aid-pros7>3.0.co;2-b
Subject(s) - medicine , alum , antibody titer , immunogenicity , adjuvant , antibody , immunization , plga , endocrinology , pharmacology , immunology , titer , chemistry , biochemistry , organic chemistry , in vitro
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. Prostate 35:279–284, 1998. © 1998 Wiley‐Liss, Inc.