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

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- conserved CD4-binding site regions of eOD-GT8 60mer to focus the antibody immune response to the CD4bs. Due to their improved antigenic and immunogenic profiles, glycan-masked eOD-GT8 60mer mutants may serve as improved priming immunogens to elicit VRC01-class broadly neutralizing antibodies in humans.

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: 

HIV-1 vaccine- the priming component in a prime-boost approach.

Competitive Advantages: 

  • Reduced off-target immunogenicity.

  • Improved efficacy in eliciting precursors for broadly neutralizing CD4bs antibodies.

  • Facilitates the development of VRC01-class bnAbs in humans.

Development Stage: In vivo testing (rodents).

Inventors: John R. Mascola (NIAID), Hongying Duan (NIAID), Xuejun Chen (NIAID), Cheng Cheng (NIAID) and Jeffrey C. Boyington (NIAID).

Publications: Duan, H. et al., Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies. Immunity 49, 301 (2018).

Intellectual Property: U.S. Provisional Patent Application Number 62/476,397 filed 03/24/2017 and PCT Application Number PCT/US2018/024330 filed 03/26/2018.

Licensing Contact: Barry Buchbinder, Ph.D., 240-627-3678; barry.buchbinder@nih.gov


NIAID Technology Transfer and Intellectual Property Office

NIAID’s technology transfer office, TTIPO, is a one-stop resource for organizations interested in partnering with NIAID to access, develop, and manage the translation of research discoveries into medically beneficial products. TTIPO seeks to expand NIAID’s innovation pipeline with existing and new partners in areas such as newly emerging and re-emerging infectious diseases (e.g., dengue, Zika, Ebola, influenza, methicillin-resistant Staphylococcus aureus and HIV/AIDS), biodefense (e.g., smallpox and anthrax), and immune-mediated diseases (e.g., asthma and allergy).

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