Improvement of Broadly HIV-Neutralizing Antibodies; Anti-HIV-1 Antibody VRC01.23 for Prevention or Treatment of HIV Infection


Scientists at NIAID have developed broadly neutralizing antibodies (bNAbs) with enhanced neutralizing activity against HIV-1. Specifically, previously unknown gp120 interactions with a newly elucidated quaternary receptor (CD4)-binding site in the HIV-1 envelope have been discovered by engrafting the extended heavy-chain framework region 3 (FR3) loop of VRC03 onto several potent bNAbs (including VRC01, VRC07 and N6). The new antibodies show improved neutralizaton of gp120 binding to CD4 by interacting with both CD4 binding sites and as a result show improved neutralization of various HIV-1 strains. Furthermore, they show reduced autoreactivity and, as a result, have prolonged in vivo half-life.

One of several antibodies that were developed using this technology is VRC01.23. It combines the VRC03 framework 3 alteration, with a G54W mutation in the heavy chain, and a 3 amino acid deletion in the light chain. The modifications improved the potency while reducing the autoreactivity. In particular, VRC01.23 is capable of neutralizing 96% of HIV-1 viruses tested at geometric mean IC50 =0.042 ug/ml, which is ~10-fold more potent than VRC01.

This technology is available for licensing for commercial development in accordance with 35 U.S.C. § 209 and 37 CFR Part 404, as well as for further development and evaluation under a research collaboration.

Potential Commercial Applications: Competitive Advantages:
  • Improving human monoclonal antibodies for HIV treatment or prevention
  • New candidates for use as a therapeutic or as a prophylactic
 
  • Interaction with multiple CD4 binding sites on gp120
  • Reduced autoreactivity when using the VRC03 framework 3 region mutation
  • Improved neutralization breadth and potency over existing antibodies
  • Extended in vivo half-life


Inventors:

Paolo Lusso (NIAID)  ➽ more inventions...

Qingbo Liu (NIAID)  ➽ more inventions...

Peter Kwong (NIAID)  ➽ more inventions...

Young Do Kwon (NIAID)  ➽ more inventions...

John Mascola (NIAID)  ➽ more inventions...


Intellectual Property:
PCT Application No. PCT/US2019/019021
US Application No. 62/633,517
US Application No. 16/971,826

Publications:
Liu, Qingbo, et al. "Improvement of antibody functionality by structure-guided paratope engraftment." Nature Communications 10.1 (2019): 721. DOI 10.1038/s41467-019-08658-4

Collaboration Opportunity:

The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Chris Kornak at chris.kornak@nih.govor 1-240-627-3705.


Licensing Contact:
Christopher Kornak, J.D.
Email: chris.kornak@nih.gov
Phone: 240-627-3705

OTT Reference No: E-034-2018-0
Updated: Mar 9, 2020