Development of a Novel Assay to Measure Antigen-Specific Immune Responses to Multivalent Vaccines for HIV-1

M. L. PETERSON*, J. W. GOOD, E. M. ZAHARIAS, S. LEE, R. SHIBATA, and P. W. BERMAN. VaxGen, Inc., Brisbane, CA

Viral diversity is a major obstacle in the development of a vaccine to fight the global HIV-1 epidemic.  To expand the breadth of response to vaccination, two bivalent subunit vaccines based upon the viral gp120 envelope protein (AIDSVAX^TM B/B and AIDSVAX^TM B/E) have been developed and are currently in Phase III testing.  In order to advance these multivalent vaccines to large scale clinical trials, it was necessary to document antigen-specific immune response to each gp120 component.  These gp120s derive from viruses from different clades (AIDSVAX^TM B/E) or from virus variants within a clade (AIDSVAX^TM B/B).  Both bivalent formulations contain gp120s from the X4- and R5-dependent phenotypes.  There is approximately 70% homology between the clade B and E gp120s comprising AIDSVAX^TM B/E and over 80% between the two clade B variants used in AIDSVAX^TM B/B. Much of the immunologic response to bivalent vaccination in animals and human clinical trial volunteers is cross-reactive between the gp120 components.  The V2 domain contains a neutralization site and is highly divergent between viral clades.  By comparing antibody response to monovalent and bivalent vaccines we demonstrated that the V2 region is immunogenic in guinea pigs, rabbits, and humans.  Antigen-specific immune responses to each of the gp120s tested were documented using synthetic V2 peptides in an indirect antibody ELISA.   In addition, we  found that the V3 domain can also distinguish between responses to the clade B and clade E derived gp120s of AIDSVAX^TM B/E, but that there is a high degree of immunogenic cross-reactivity to this region between the more closely related clade B variants in AIDSVAX^TM B/B.  Nevertheless, we found a heterologous V3 sequence from a common clade B virus which can be used to distinguish specific immunogenicity of one of the AIDSVAX^TM B/B components. The V2 peptide assays described represent a generic assay strategy to document antigen-specific immune responses in virtually any multivalent vaccine based upon gp120.

Key Words: gp120, immunogenicity, vaccine

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