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Rational Design of Live Attenuated Influenza A Vaccine Candidates

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
Program Year/Program:
2012 / STTR
Agency Tracking Number:
R41AI100428
Solicitation Year:
2012
Solicitation Topic Code:
NIAID
Solicitation Number:
PA10-124
Small Business Information
CODAGENIX, INC.
7 GAY DR GREAT NECK, NY -
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2012
Title: Rational Design of Live Attenuated Influenza A Vaccine Candidates
Agency: HHS
Contract: 1R41AI100428-01
Award Amount: $600,000.00
 

Abstract:

DESCRIPTION (provided by applicant): Despite the availability of influenza vaccines, approximately 35,000 individuals die each year in the US alone from influenza, and influenza-related complications. The clinical impact of Influenza motivates the search for new, more effective vaccines that can be rapidly designed and easily produced. We have developed a rational, computer-aided approach to construct efficacious live attenuated (weakened) influenza virus vaccine candidates. The process is termed SyntheticAttenuated Virus Engineering (SAVE), (Coleman et al., 2008. Science 320(5884):1784-7) The custom designed attenuation used in the SAVE technology operates through genome-scale changes in codon pair bias (Mueller et al., 2010. Nature Biotechnology 28:723-727). In this proposal, we will extend our technology, which successfully created a live-attenuated vaccine in the laboratory strain A/PR8/3/34 (Mueller et al. 2010), to a clinically significant pandemic influenza strain, A/California/07/2009 (CA07). CA07 was the strain responsible for the 2009 H1N1 ( swine flu ) pandemic. These SAVE-attenuated (weakened) CA07 viruses will be tested for their level of safety and their potential as live vaccine candidates in a mouse model. Attenuation in our system is achieved via designing hundreds of synonymous nucleotide changes across the viral genome. This rational gene design approach allows Codagenix Inc. to maintain the amino acid sequences to have 100% identity to all viral proteins. These hundreds of mutations offers a wide margin of safety for vaccine candidates via high genetic stability. Also maintaining a 100% amino acid sequence match to the vaccine target, provides a characteristic of SAVE-attenuated vaccines that is not present in any currently available vaccine technology. By extending SAVE to a strain of clinical importance, as well as constructing various synthetic designs, we will show that our unique computer algorithms allow us construct viable vaccine candidates with the additional ability to tune theamount of attenuation predictably, similar to the volume on a car radio. Given that SAVE is a computer-aided approach the method can be applied rapidly to any emerging influenza virus in its entirety. The deliverable of this project is an improved live attenuated vaccine strain of the A/California/07/2009 lineage that has 100% amino acid identity to the target strain. This vaccine candidate will be taken into further clinical development in Phase II. PUBLIC HEALTH RELEVANCE: Vaccination has beenhumankind's main most robust defense against viral disease. We describe an entirely novel and rapid method to generate anti-Influenza A vaccine candidates that might prove applicable to most if not all Influenza A strains.

Principal Investigator:

Eckard Wimmer
516-689-6000
ewimmer@ms.cc.sunysb.edu

Business Contact:

Steffen Mueller
516-567-5888
mueller@codagenix.com
Small Business Information at Submission:

CODAGENIX, INC.
7 GAY DR GREAT NECK, NY -

EIN/Tax ID: 126446093
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
Research Institution Information:
STATE UNIVERSITY NEW YORK STONY BROOK
STONY BROOK UNIVERSITY
The Office of Sponsered Programs Melville Library Room 5501W
STONY BROOK, NY 11794-
Contact: