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CMCC 2196

Novel HIV Vaccine Immunogens for Eliciting Neutralizing Antibodies

Inventors: Bing Chen, Gary Frey, Jia Chen

Invention Types: Diagnostic/Prognostic, Therapeutics

Research Areas: Infectious Disease

Keywords: Protein, Vaccine

For More Information Contact:  Caron, Connie

 

Invention Description:

HIV/AIDS is a major global epidemic affecting 0.8% of worldwide population and causing ~2 million deaths each year in the entire world. As of the end of 2009, approximately 36 million persons worldwide were living with HIV/AIDS, of which 2.5 million were newly infected during the year. A successful HIV vaccine has been elusive, due to the failure to produce an immunogen that elicits the robust production of protective, neutralizing antibodies in the recipient.

Dr. Chen's group, building on previous work in collaboration with Dr. Stephen Harrison, has developed a protein structure-based paradigm to HIV vaccine design, incorporating the understanding of the dynamic changes in protein structure that occur on viral entry into the cell. The inventors have created stable protein constructs from the HIV-1 gp41 protein locked in specific conformations. They have demonstrated that the dominant, non-neutralizing antibodies produced in an immune response bind to a post-fusion conformation. This post-fusion conformation may represent an immunological decoy, stimulating the production of ineffective antibodies. Neutralizing antibodies, on the other hand, bind tightly to a transient intermediate conformation which is exposed only during viral fusion. They have further refined the stable gp41 protein construct exposing the fusion intermediate state conformation, and demonstrate that neutralizing antibodies bind specifically and tightly to this antigen.

Applications:

• Immunogens for an HIV vaccine for eliciting robust neutralizing antibody production.
• Antigens to assess the presence and titer of neutralizing antibodies in a patient.
• Therapeutic screening reagents for viral entry inhibitors

Competitive Advantages:

Current AIDS treatment (HAART) is expensive and offers no cure. A preventive vaccine is greatly needed, in particular for developing countries where costly medicines are often unavailable and disease transmission continues unchecked. Currently, no one has successfully developed an HIV vaccine.

Business Opportunity:

• Exclusive or non-exclusive license to a company with existing HIV vaccine development pipeline
• Sponsored Research

Key Publications: Distinct conformational states of HIV-1 gp41 are recognized by neutralizing and non-neutralizing antibodies.
Frey G, Chen J, Rits-Volloch S, Freeman MM, Zolla-Pazner S, Chen B.
Nat Struct Mol Biol. 2010 Dec;17(12):1486-91.

http://www.ncbi.nlm.nih.gov/pubmed/21076402

IPStatus: Pat. Pend.