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Glycan-masked Engineered Outer Domains of HIV-1 GP120 and Their Use: Collaborative and Licensing Opportunity

Newly invented glycan-masked eOD-GT8 60mer mutants may serve as improved priming immunogens to elicit VRC01-class bnAbs in humans.

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Nature Research Custom Media
NIAID Technology Transfer and Intellectual Property Office

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.

• Reduced off-target immunogenicity.

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

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

Competitive Advantages:

Development Stage: In vivo testing (rodents).

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: HHS Reference Number E-083-2017 includes 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

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