Novel System for HIV-1 Vaccine Development


The available technologies describe specific immunogenic peptides, peptide modifications and methods for identifying additional immunogens against HIV-1 surface proteins, gp120 and gp41. Additionally, detailed methods for use of the described immunogenic peptides in the development of vaccines and diagnostics for HIV-1 are disclosed. The current technologies further include a comprehensive system for immunogen design, comprising in silico design coupled to feedback from X-ray crystallography, antigenic analysis, and immunization.

The described methodology demonstrates how to transplant a given HIV-1 epitope recognized by broadly neutralizing antibodies into an appropriate scaffold, while preserving its structure and antigenicity. Conservation of the three dimensional structure may lead to the generation of antibodies with broadly neutralizing characteristics, similar to the template antibody. Such epitope-transplant scaffolds may serve as valuable diagnostics to identify specific serum reactivity against the target HIV-1 epitopes. The subject scaffolding technology may be applied to any virus for which a broadly neutralizing antibody and its respective epitope has been characterized at the atomic-level.

Potential Commercial Applications: Competitive Advantages:
  • Immunogens that elicit immune responses to HIV-1
  • Efficient development of vaccines against HIV-1
  • Screening tool to isolate antibodies with activities similar to identified template antibody
 


Inventors:

Peter Kwong (NIAID)  ➽ more inventions...


Intellectual Property:
U.S. Pat: 8,715,686 issued 2014-05-06
U.S. Pat: 8,044,185 issued 2011-10-25
U.S. Pat: 8,147,840 issued 2012-04-03
U.S. Pat: 8,268,323 issued 2012-09-18
US Application No. 60/570,883
US Application No. 60/840,119
US Application No. 12/065,883
US Application No. 12/065,894
US Application No. 11/596,494
US Application No. 13/232,775

Publications:
G Ofek, W Schief, J Guenaga, et al. Epitope-transplant scaffolds: automated design, structural analysis, and antigenic characteristics. Manuscript in preparation (2007). PubMed abs
T Zhou, L Xu, B Dey, AJ Hessell, DV Ryk, SH Xiang, X Yang, MY Zhang, MB Zwick, J Arthos, DR Burton, DS Dimitrov, J Sodroski, R Wyatt, GJ Nabel, PD Kwong. Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature. 2007 Feb 15;445(7129):732-737. PubMed abs
DC Douek, PD Kwong, GJ Nabel. The rational design of an AIDS vaccine. Cell. 2006 Feb 24;124(4):677-681. PubMed abs
G Ofek, M Tang, A Sambor, H Katinger, JR Mascola, R Wyatt, PD Kwong. Structure and mechanistic analysis of the anti-HIV-1 antibody 2F5 in complex with its gp41 epitope. J Virol. 2004 Oct;78(19):10724-10737.

Licensing Contact:
Barry Buchbinder, Ph.D.
Email: BBuchbinder@niaid.nih.gov
Phone: 301-496-2644

OTT Reference No: E-218-2004-0
Updated: Mar 1, 2007