Glycan-masked engineered outer domains of HIV-1 GP120 and Their Use


The VRC01-class of potent, broadly neutralizing antibodies (bnAbs) targets the conserved CD4-binding site (CD4bs) of HIV-1 Env which has been a major target of HIV-vaccine design. The current best priming immunogen to engage the VRC01-class germline precursors is the eOD-GT8 60mer, which elicits VRC01-class precursors in multiple transgenic mouse models. However, a large proportion of the antibodies elicited by eOD-GT8 60mer are non-CD4bs or “off-target” antibodies, undermining its effectiveness in eliciting the VRC01-class bnAb precursors.

Researchers at the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases introduced multiple N-linked glycosylation sites to mask non-CD4bs regions of eOD-GT8 60mer to focus the antibody immune response to the CD4bs.

Several glycan-masked mutants showed significantly decreased antibody binding to non-CD4bs “off-target” epitopes while maintaining strong binding to CD4bs-specific bnAbs. Furthermore, in vivo studies showed that immunization with the best glycan-masked eOD-GT8 mutants resulted in significant increases in the elicitation of CD4bs-specific serum antibodies, CD4bs-specific B cells in the spleen, and VRC01-class precursors, compared to immunization with the parental eOD-GT8 immunogen. In conclusion, because of their improved antigenic and immunogenic profiles, glycan-masked eOD-GT8 60mer mutants may serve as improved priming immunogens to elicit VRC01-class bnAbs in humans.

Potential Commercial Applications: Competitive Advantages:
  • HIV-1 vaccine- the priming component in a prime-boost approach.
 
  • Reduced off-target immunogenicity.
  • Improved efficacy in eliciting precursors for broadly neutralizing CD4bs antibodies
  • Facilitates the development of VRC01-class bnAbs in humans.


Inventors:

Xuejun Chen (NIAID)  ➽ more inventions...

Cheng Cheng (NIAID)  ➽ more inventions...

Jeffrey Boyington (NIAID)  ➽ more inventions...

John Mascola (NIAID)  ➽ more inventions...

Hongying Duan (FDA)  ➽ more inventions...


Intellectual Property:
US Application No. 62/476,397
PCT Application No. PCT/US2018/024330

Publications:
Duan, H. et al. PMID: 201807005

Collaboration Opportunity:

For collaboration opportunities, please contact Barry Buchbinder, PhD at barry.buchbinder@nih.govor 1-240-627-3678.


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

OTT Reference No: E-083-2017-0
Updated: Oct 12, 2018