Substitutions-modified Prefusion RSV F Proteins and their Use: Collaboration and Licensing Opportunity

Researchers at the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases have overcome technical obstacles to produce a homogeneous, soluble RSV F glycoprotein vaccine which is stabilized in the prefusion conformation and has improved stability and immunogenicity compared to the native protein. Additionally, several modifications were introduced to remove the requirement for furin during production, resulting in an increase in expression levels of the immunogen.

The respiratory syncytial virus (RSV) fusion (F) glycoprotein is the primary target of neutralizing antibodies. The F glycoprotein exists in at least two conformations, a meta-stable prefusion state, and an extremely stable postfusion state. Both states share several epitopes targeted by neutralizing antibodies, but it has been demonstrated that the prefusion conformation of F contains at least one epitope not present in the postfusion conformation. Natural infection results in neutralizing antibodies that are primarily directed against the prefusion conformation of F, not its postfusion conformation. The instability of the prefusion form of F has hindered both its characterization and its use as a vaccine antigen.

Researchers at the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases have overcome technical obstacles to produce a homogeneous, soluble RSV F glycoprotein vaccine which is stabilized in the prefusion conformation and has improved stability and immunogenicity compared to the native protein. Additionally, several modifications were introduced to remove the requirement for furin during production, resulting in an increase in expression levels of the immunogen. Stability of the immunogen was increased 20-fold as compared to DS-CAV1 (a prefusion-stabilized RSV F glycoprotein vaccine candidate that is currently being assessed in clinical trials) upon incubation at 60 ºC. In mice, these immunogens elicited neutralization titers that were 2 to 5-fold higher than DS-CAV1. 

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: 

  • Vaccine: RSV vaccine for human use.

  • Probe: B cell-sorting probe to isolate potent neutralizing monoclonal antibodies

  • Diagnostics: To assess the titer of prefusion-specific antibodies in sera.

Competitive Advantages: 

  • Increased stability compared to the current leading RSV vaccine candidate (DS-Cav1).

  • Elicits increased neutralization titers in mice.

Development Stage:

  • In vivo testing (mice)

Inventors:   Peter D. Kwong (NIAID), M. Gordon Joyce (NIAID), Baoshan Zhang (NIAID), Man Chen (NIAID), Barney S. Graham (NIAID), John R. Mascola (NIAID), Aliaksandr A. Druz (NIAID), Wing-Pui Kong (NIAID), Ivelin Georgiev (NIAID), Yaroslav Tsybovsky (Leidos Biomedical Research), Paul V. Thomas (NIAID), Marie L. Pancera (NIAID), Mallika Sastry (NIAID), Cinque Soto (NIAID), Guillaume B.E. Stewart-Jones (NIAID), Yongping Yang (NIAID), Li Ou (NIAID), Ulrich Baxa (NCI), Emily Rundlet (NIAID), Joseph Van Galen (NIAID).

Publications:  Joyce, M. Gordon, et al., Nature structural & molecular biology, 23.9 (2016): 811; PMID: 27478931

  Intellectual Property: U.S. Patent Application No. 62/314,946 filed 03/29/2016; PCT Application Number PCT/US2017/024714 filed 03/29/2017 (pending)

Licensing Contact: Vince Contreras, PhD, 240-669-2823; vince.contreras@nih.gov


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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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