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Influenza Vaccines, Therapeutics, and Monoclonal Antibodies

Posted Oct 20 2009 5:00pm

Description of Invention:
Concerns about a potential influenza pandemic and its prevention are a regular part of health news, with bird (avian) influenza (prominently including H5N1 strains) being a major concern. Vaccination is one of the most effective ways to minimize suffering and death from influenza. Currently, there is not an effective way to vaccinate against avian influenza without knowing what subtype and strain will circulate. Described here are two technologies with application to development of vaccines against influenza as well as therapeutics and monoclonal antibodies. One technology provides for development of potentially broadly protective influenza vaccines, while the other seeks to improve immune response to the vaccine through increased receptor affinity.

The first technology offers candidate DNA vaccines that were primarily designed to elicit neutralizing antibodies to target H5N1, H1N1, H3N2 and other subtypes of influenza. The candidate vaccines express H/HA or neuramidase (N/NA) protein that has been codon optimized and/or modified at the protease cleavage site. The modified genes could be used in DNA vaccines, in viral vectors, recombinant proteins/particles or combination. Exemplary animal studies use proprietary expression systems that increase protein expression relative to commonly used alternatives. This invention potentially provides a vaccine strategy for controlling influenza epidemics, including avian flu, should it cross over to humans; the 1918 strain of flu; and seasonal flu strains. In addition, this invention is designed to lead to a combination vaccine to provide a broadly protective vaccine.

The second technology relates to H5N1 influenza vaccine candidates in which mutations have been introduced to increase affinity of the hemagglutinin (H or HA) for the sialic acid receptor found in humans, which have a different sialic acid linkage than the corresponding avian receptor. These mutations could therefore result in a higher immune response in vaccines, producing a more robust response than other H5N1 vaccine candidates that retain their avian receptor preferences. These mutations also changed antibody-sensitivity of the vaccine candidates. The H5 modifications can be expressed from DNA or adenoviral vectors, or the proteins themselves can be administered. Additionally, these mutated HAs can be used to develop therapeutic monoclonal antibodies. The technology describes three (3) unique monoclonal antibodies that react with wild-type H5, wild-type H5 and mutant HA equivalently, and the mutant HA, respectively.

Applications:
  • Influenza vaccine for pandemic or epidemic application
  • Therapeutic antibodies
  • Potential for combination vaccine for broad protection, removing need for seasonal strain monitoring


Advantages:
  • DNA vaccines are easy to produce and store
  • No risk of reversion to pathogenic strain as with live-attenuated virus vaccines


Development Status:
  • Phase I clinical trial active for DNA vaccine candidate encoding H5, Indonesian strain (VRC-AVIDNA-036-00VP)
  • Animal (mouse) data available
  • Codon optimized for expression in human cells


Inventors:
Gary J Nabel (NIAID)
Zhi-yong Yang (NIAID)
Wing-pui Kong (NIAID)
Lan Wu (NIAID)
Chih-jen Wei (NIAID)


Patent Status:
HHS, Reference No. E-116-2006/1
PCT, Application No. PCT/US2007/004506 filed 16 Feb 2007
US, Application No. 12/279,332 filed 13 Aug 2008 (Corresponding National Stage Patent Applications filed in Canada, Europe, India, China, S. Korea, and Singapore)
PCT, Application No. PCT/US2007/081002 filed 10 Oct 2007
US, Application No. 12/443,964 filed 01 Apr 2009


Related Technologies:
US, Patent No. 7,094,598, Issued 22 Aug 2006, Reference No. E-241-2001/1 and associated foreign rights (proprietary expression system with CMV/R promoter)


Relevant Publication:
  1. CJ Wei, L Xu, WP Kong, W Shi, K Canis, J Stevens, ZY Yang, A Dell, SM Haslam, IA Wilson, GJ Nabel. Comparative efficacy of neutralizing antibodies elicited by recombinant hemagglutinin proteins from avian H5N1 influenza virus. J Virol. 2008 Jul;82(13):6200-6208. [ PubMed abs ]
  2. WP Kong, C Hood, ZY Yang, CJ Wei, L Xu, A Garcia-Sastre, TM Tumpey, GJ Nabel. Protective immunity to lethal challenge of the 1918 pandemic influenza virus by vaccination. Proc Natl Acad Sci USA. 2006 Oct 24;103(43):15987-15991. [ PubMed abs ]
  3. GJ Nabel. Gene-based influenza vaccines: a look to the future. Presentation to World Health Organization (WHO), February 2007; available online at http://www.who.int/vaccine_research/diseases/influenza/160207_Nabel.pdf. [ Nabel WHO presentation ]


Licensing Status:
Available for non-exclusive or exclusive licensing.


Portfolios:
Infectious Diseases
Infectious Diseases - Therapeutics
Infectious Diseases - Vaccines



For Additional Information Please Contact:
Cristina Thalhammer-Reyero Ph.D., M.B.A.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325 Room 33,
Rockville, MD 20852
United States
Email: thalhamc@mail.nih.gov
Phone: 301-435-4507
Fax: 301-402-0220


Ref No: 1547

Updated: 10/2009

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