Novel Fusion Proteins for HIV Vaccine


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.



Potential Commercial Applications: Competitive Advantages:
  • As an immunogen in an HIV vaccine
  • Research tools to study the conformational flexibility of gp120, the mechanisms of viral entry, and evasion of immune responses
 
  • The potential vaccine immunogens could be more efficient than gp120 alone
  • Higher affinity for CD4 than gp120 alone, with antibodies directed against the CD4-binding site


Development Stage:
Discovery (Lead Identification)

Inventors:

Dimiter Dimitrov (NCI)  ➽ more inventions...


Intellectual Property:

Publications:
Dey B, et al. Structure-based stabilization of HIV-1 gp120 enhances humoral immune responses to the induced co-receptor binding site. PMID 19478876
Dey B, et al. Characterization of human immunodeficiency virus type 1 monomeric and trimeric gp120 glycoproteins stabilized in the CD4-bound state: antigenicity, biophysics, and immunogenicity.  PMID 17360741

Collaboration Opportunity:

Licensing only


Licensing Contact:
John Hewes, Ph.D.
Email: John.Hewes@nih.gov
Phone: 240-276-5515

OTT Reference No: E-256-2012
Updated: Sep 6, 2016