ANTIBODIES WITH SPECIFICITY TO NATIVE GP120 AND NEUTRALIZATION ACTIVITY AGAINST PRIMARY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATES ELICITED BY IMMUNIZATION WITH OLIGOMERIC GP160

Current human immunodeficiency virus type I (HIV-I) envelope vaccine c andidates elicit high antibody binding titers with neutralizing activi ty against T-cell line-adapted but not primary HIV-1 isolates. Serum a ntibodies from these human vaccine recipients were also found to be pr eferentially directed to linear epitopes within gp120 that are poorly exposed on native gp120. Systemic immunization of rabbits with an affi nity-purified oligomeric gp160 protein formulated with either Alhydrog el or monophosphoryl lipid A-containing adjuvants resulted in the indu ction of high-titered serum antibodies that preferentially bound epito pes exposed on native forms of gp120 and gp160, recognized a restricte d number of linear epitopes, efficiently bound heterologous strains of monomeric gp120 and cell surface-expressed oligomeric gp120/gp41, and neutralized several strains of T-cell line-adapted HIV-1. Additionall y, those immune sera with the highest oligomeric gp160 antibody bindin g titers had neutralizing activity against some primary HIV-1 isolates , using phytohemagglutinin-stimulated peripheral blood mononuclear cel l targets. Induction of an antibody response preferentially reactive w ith natively folded gp120/gp160 was dependent on the tertiary structur e of the HIV-1 envelope immunogen as well as its adjuvant formulation, route of administration, and number of immunizations administered. Th ese studies demonstrate the capacity of a soluble HIV-1 envelope glyco protein vaccine to elicit an antibody response capable of neutralizing primary HIV-1 isolates.