Abstract # I-19
Immunogenicity of Viral Protein Antigens. I. Berkower1, J. Patterson2, and A. Aberdeen.1 1CBER, FDA, Bethesda, MD, 2NCI
Previous work with HIV has shown that an important and broadly reactive target of neutralizing antibodies is located on envelope glycoprotein gp120 near the CD4 binding site and depends on native conformation. Other parts of gp120 can be substituted with SIV sequences or truncated at the NH2 end without losing these sites. We have now truncated the NH2 end and replaced it with other sequences from a more immunogenic protein, core antigen of hepatitis B virus. This sequence contains important sites for helper T cell recognition and self assembly and can act as a proteinprotein carrier. The hybrid contains a core antigen insert in the correct location and orientation, as shown by PCR, and gp120 antigenicity was shown on western blot. Immunoprecipitation with CD4Ig demonstrated a functional CD4 binding site, suggesting that the hybrid protein contained the neutralizing site as well. Vaccinia recombinants will express the hybrid protein in sufficient amounts to test self assembly and immunogenicity. By combining the antigenicity of the gp120 neutralizing epitope with the immunogenicity of core antigen, hybrids at the insert acceptor site may overcome the relatively weak immune response to current HIV vaccines and elicit neutralizing antibodies to a broad spectrum of HIV isolates.