Technology Bundle ID: TAB-3323

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

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Primary Inventors: 
Xuejun Chen (NIAID)
Co-Inventors: 
Cheng Cheng (NIAID), Hongying Duan (FDA), Jeffrey Boyington (NIAID), John Mascola (NIAID)
Institute or Center: 
NIAID

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.

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

Patents

PCT Application PCT/US2018/024330
Filed on 2018-03-26
US Application 16/496,912
Filed on 2019-10-02
US Application 62/476,397
Filed on 2017-03-24

Publications

Duan, H. et al.
PMID: 201807005

Updated

Oct 12, 2018

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