We have expressed gp120 in vaccinia recombinants and made hybrids containing foreign sequences inserted at specific sites into structures containing 180-24- copies of gp120 hybrid. Two hybrids made dual antigenicity for gp120 and the insert, bind CD4, and at least partially assembled multimers. They behave as dual antigens, since they elicit antibodies to both hyrid and boost antibodies to gp120 twenty-fold when primed with the insert. They show promise for enhancing the intrinsic immunogenicity of gp120 vaccines. Full constructs favor self-assembly by reducing steric hindrance or providing free stabilized multimers via interchain disulfide bonds. Despite the urgent need for an HIV vaccine in the U.S. and the world. Our program has proceeded in a stepwise fashion to neutralizing sites on gp120 and make constructs with enhanced potency, The constructs will help CBER understand the factors limiting potency currently available HIV vaccines as well as the recombinant vaccines. They also contribute to understanding the correlates of protection. These studies will evaluate HIV vaccine trials ongoing as well as those planned for the future.
