A Universal Antigen Delivery Platform for Enhanced Immune Response

Description of Invention:
The present invention relates to use of the rotavirus NSP2 octamer as a universal antigen delivery platform for presenting a high density of neutralizing epitopes to the immune system, a strategy for boosting antigen immunogenicity. This application is advanced by the well-defined structural and biochemical properties of the octamer, its high stability at a broad range of pH, temperature and ionic stability, and its ease of purification (one step) under nondenaturing conditions. Long conformationally-dependent antigens are readily mounted onto the platform by fusion to the C-terminus of NSP2, a region of the NSP2 protein positioned on the exposed surface of the octamer. The platform can be expressed in and purified from prokaryotic and eukaryotic systems.

This technology can be used for rapid production of subunit vaccines against a wide range of infectious agents. Additional uses of the technology include the generation of delivery platforms with mounted short peptide antigens for use in cancer immunotherapy, production of specific antisera to conformationally and nonconformationally-dependent antigens for research purposes, and development of epitope targets and short peptide-antigen presentation platforms for diagnostic assays.

Applications:

• Vaccines against pathogens
• Cancer vaccines
• Antigen-specific antisera
• Multivalent targets in diagnostic assays

Advantages:

• Octameric platform is stable, efficiently expressed, and easily purified by a single step method
• Enables the display of multivalent conformation-dependent epitopes
• Effective platform for short peptides as well as long polypeptides

Development Status:
Proof-of-concept experiments have shown that the octamer mounted with short peptides or long multivalent polypeptides retains its structural and biophysical features and is highly effective in presenting foreign antigens to the immune system. Ease of purification and final protein yields of the short or long peptide antigen-mounted NSP2 octamers were comparable suggesting that the platform accommodates a large range of antigen sizes. The NSP2-platform also served as an adjuvant, significantly enhancing immunity of the mounted peptide.

Inventors:
John T Patton (NIAID)
Zenobia F Taraporewala (NIAID)


Patent Status:
HHS, Reference No. E-322-2004/0
US, Application No. 11/293,654 filed 02 Dec 2005


Relevant Publication:

1. P Schuck et al. Rotavirus nonstructural protein NSP2 self-assembles into octamers that undergo ligand-induced conformational changes. J Biol Chem. 2001 Mar 30;276(13):9679-9687. [ PubMed: 11121414 ]
2. H Jayaram et al. Rotavirus protein involved in genome replication and packaging exhibits a HIT-like fold. Nature. 2002 May 16;417(6886):311-315. [ PubMed: 12015608 ]
3. Z Taraporewala et al. Rotavirus NSP2 octamer as an epitope-mounting platform. Abstract, 23rd Annual Meeting of the American Society for Virology, 2004.
4. K Kearney et al. Cell-line-induced mutation of the rotavirus genome alters expression of an IRF3-interacting protein. EMBO J. 2004 Oct 13;23(20):4072-4081. [ PubMed: 15372078 ]

Licensing Status:
Available for licensing.


Portfolios:
Infectious Diseases
Infectious Diseases - Vaccines



For Licensing Information Please Contact:
Kevin Chang Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: changke@mail.nih.gov
Phone: 301-435-5018
Fax: 301-402-0220


Ref No: 1080

Updated: 12/2010