The search for an AIDS vaccine has been complicated by the high degree of genetic variation that characterizes the Human Immuno-deficiency Virus (HIV). In a prototype study of 20 different HIV, we found that isolates could be grouped into four distinct classes according to their biological properties and their sensitivity to serum neutralization in vitro. To assess the potential number of independent serotypes among the HIV isolated in our laboratory, we propose to confirm these initial results and to evaluate other HIV. Antisera to isolates selected from the four neutralization-specific groups are now being produced in guinea pigs. The sera obtained thus far show reactivity to both viral recombinant gag and env proteins by indirect ELISA. These strain-specific antisera will be used in neutralization as well as cytotoxicity and plaque inhibition assays to extend further the serotypic classification of HIV. Based on the results of this prototype study, the serotyping of a larger number of biologically cloned HIV of various geographical origin and with different biological features will be undertaken. Subsequently, the purified envelope glycoprotein (gp120) of isolates representative of the different serotypes defined will be used to immunize guinea pigs to confirm the existence and to localize serotypic determinants on the HIV envelope. The HIV selected will be then be used for preparation (Dr. Steimer, Chiron Corporation; Dr. Luciw, UC Davis) and testing (Dr. Gardner, et al, UC Davis) of candidate vaccines in guinea pigs and Rhesus monkeys. The vaccine materials obtained in this manner can be utilized for efficacy study in chimpanzees (Dr. Eichberg, Southwest Foundation). The outcome of this proposed research will be important for the design and preparation of an effective vaccine for AIDS.