Development of Mutations Useful for Attenuating Dengue Viruses and Chimeric Dengue Viruses
Posted Sep 30 2008 5:00pm
Description of Invention: Although flaviviruses cause a great deal of human suffering and economic loss, there is a shortage of effective vaccines. This invention relates to dengue virus mutations that may contribute to the development of improved dengue vaccines. Site directed and random mutagenesis techniques were used to introduce mutations into the dengue virus genome and to assemble a collection of useful mutations for incorporation in recombinant live attenuated dengue virus vaccines. The resulting mutant viruses were screened for several valuable phenotypes, including temperature sensitivity in Vero cells or human liver cells, host cell restriction in mosquito cells or human liver cells, host cell adaptation for improved replication in Vero cells, and attenuation in mice or in mosquitoes. The genetic basis for each observed phenotype was determined by direct sequence analysis of the genome of the mutant virus. Mutations identified through these sequencing efforts have been further evaluated by re-introduction of the identified mutations, singly, or in combination, into recombinant dengue virus and characterization of the resulting recombinant virus for phenotypes. In this manner, a menu of attenuating and growth promoting mutations was developed that is useful in fine-tuning the attenuation and growth characteristics of dengue virus vaccine candidates. The mutations promoting growth in Vero cells have usefulness for the production of live or inactivated dengue virus vaccines.
Inventors: Stephen S Whitehead (NIAID) Brian R Murphy (NIAID) Kathryn A Hanley (NIAID) Joseph E Blaney (NIAID)
Collaborative Research Opportunity: The National Institute of Allergy and Infectious Diseases, Laboratory of Infectious Diseases, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these vaccines. Please contact Dr. Brian Murphy at 301-594-1616 or bm25f@nih.gov for more information.
For Additional Information Please Contact: Peter Soukas J.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325
Room 14, Rockville, MD 20852-3804 United States Email: soukasp@mail.nih.gov Phone: 301-435-4646 Fax: 301-402-0220
Description of Invention:
Although flaviviruses cause a great deal of human suffering and economic loss, there is a shortage of effective vaccines. This invention relates to dengue virus mutations that may contribute to the development of improved dengue vaccines. Site directed and random mutagenesis techniques were used to introduce mutations into the dengue virus genome and to assemble a collection of useful mutations for incorporation in recombinant live attenuated dengue virus vaccines. The resulting mutant viruses were screened for several valuable phenotypes, including temperature sensitivity in Vero cells or human liver cells, host cell restriction in mosquito cells or human liver cells, host cell adaptation for improved replication in Vero cells, and attenuation in mice or in mosquitoes. The genetic basis for each observed phenotype was determined by direct sequence analysis of the genome of the mutant virus. Mutations identified through these sequencing efforts have been further evaluated by re-introduction of the identified mutations, singly, or in combination, into recombinant dengue virus and characterization of the resulting recombinant virus for phenotypes. In this manner, a menu of attenuating and growth promoting mutations was developed that is useful in fine-tuning the attenuation and growth characteristics of dengue virus vaccine candidates. The mutations promoting growth in Vero cells have usefulness for the production of live or inactivated dengue virus vaccines.
Inventors:
Stephen S Whitehead (NIAID)
Brian R Murphy (NIAID)
Kathryn A Hanley (NIAID)
Joseph E Blaney (NIAID)
Patent Status:
HHS, Reference No. E-120-2001/0
US, , Patent No. 7,226,602, Issued 05 Jun 2007
US, , Patent No. 7,560,118, Issued 14 Jul 2009
PCT, Application No. PCT/US02/16308 filed 22 May 2002
US, Application No. 12/396,376 filed 02 Mar 2009
Licensing Status:
Available for licensing.
Collaborative Research Opportunity:
The National Institute of Allergy and Infectious Diseases, Laboratory of Infectious Diseases, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize these vaccines. Please contact Dr. Brian Murphy at 301-594-1616 or bm25f@nih.gov for more information.
Portfolios:
Infectious Diseases
Infectious Diseases - Vaccines
Rare Diseases
Neglected Diseases
For Additional Information Please Contact:
Peter Soukas J.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325 Room 14,
Rockville, MD 20852-3804
United States
Email: soukasp@mail.nih.gov
Phone: 301-435-4646
Fax: 301-402-0220
Ref No: 535
Updated: 10/2008