The preparation, characterization and pre-clinical evaluation of an orally administered HIV-I vaccine, consisting of a branched peptide immunogen entrapped in controlled release microparticles

Abstract

A microencapsulated vaccine was prepared, containing a branched peptide immunogen (200M), representing a portion of the principal neutralizing determinant of HIV-1, entrapped in poly (lactide-co-glycolide) microparticles. Following extensive in vitro characterization of the microparticles, which included assessments of particle size and size distributions, microparticle surface structure, antigen loading level and efficiency of entrapment, moisture content, the levels of residual solvent, the in vitro release rate, an assessment of antigen integrity, the product bioburden and stability during storage, the microparticles were assessed in vivo. The initial assessments undertaken, involved studies in different animal species to determine the safety and pyrogenicity of the vaccine and also the toxicity following oral administration. Once the microparticles had been shown to be safe, pyrogen free and non-toxic, they were assessed for their ability to induce serum IgG and neutralizing antibody responses in guinea pigs. Following oral immunization alone, and combined oral and subcutaneous immunization, the microparticles were shown to induce high levels of both serum IgG and neutralizing antibodies against HIV. Pending review by the U.S. Food and Drugs Administration, the microparticle based oral vaccine against HIV-1 will be assessed in clinical trials in seronegative human volunteers.