Discovery (Lead Identification)
Development of successful HIV vaccine immunogens continues to be a major challenge. Although gp120 was identified as having significant potential as a vaccine immunogen, attempts to elicit broadly neutralizing antibodies using recombinant gp120 failed. The highly flexible gp120 may present numerous conformations to the humoral immune system that are not found on the viral spike. Therefore, they elicit antibodies that bind to recombinant gp120, but do not neutralize genetically diverse viruses. The presence of highly immunogenic non-neutralizing epitopes on gp120 may distract the immune system from response to conserved neutralizing epitopes, such as the CD4 binding site.
The National Cancer Institute’s Cancer and Inflammation Program researchers improved the recognition of the HIV-1 gp120 CD4 binding site (CD4bs) by CD4 and antibodies targeting the CD4bs by fusing the gp120 to CD4-induced (CD4i) antibodies. These novel fusion proteins (CD4i antibody-gp120) may be useful as potential vaccine immunogens that could be more efficient in eliciting the broadly neutralizing antibodies against HIV-1, or potentially as candidate HIV-1 therapeutics.