Mechanisms for Improving the Breadth of the Immune Response to Diverse Strains and Clades of HIV


This technology describes a multiclade Env vaccine candidate that elicited neutralizing antibodies to a diverse group of primary HIV-1 isolates as compared to antibodies generated from immunization with single clade vaccines. The immunogens of the vaccine included V3 loops from clades A, B, and C and had the cleavage site, fusion peptide, and interhelical regions deleted. Competition studies suggested that the neutralization activity is directed toward shared, conserved epitopes other than the V3 loop. Also described in this technology are immunogens involving deletion of the V3 loop that generated more potent neutralizing antibodies, suggesting that the highly conserved subregions within V3 may be relevant targets to elicit neutralizing antibody responses and increase the immunogenicity of HIV/AIDS vaccines. Such selective deletions in the V3 loop are effective in combination with deletions of other V loops. Immunogens with deletions of the V regions in general (V1 - V4), including combinations of deletion immunogens, were also shown to elicit potent neutralizing antibodies. Previous studies of the cell-mediated immune response in mice using the multiclade vaccines of this current technology have shown that they induce Env-specific CD4 and CD8 immune response to multiple clades. Thus, this technology offers promise in developing a globally effective HIV/AIDS vaccine, which must induce both cellular and humoral immunity to multiple strains from the various clades.

This work is described, in part, in Z. Yang et al., J. Virol. (April 2004) 78(8): 4029-4036.



Inventors:

Gary Nabel (NIAID)  ➽ more inventions...


Intellectual Property:
U.S. Pat: 7,947,822 issued 2011-05-24
PCT Application No. 11/376,484
US Application No. 12/683,844

Licensing Contact:
Carol Salata, Ph.D.
Email: csalata@mail.nih.gov
Phone: 240-627-3727

OTT Reference No: E-335-2003-0
Updated: Jun 1, 2004