Rational Design of Live Attenuated Influenza A Vaccine Candidates

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$600,000.00
Award Year:
2012
Program:
STTR
Phase:
Phase I
Contract:
1R41AI100428-01
Award Id:
n/a
Agency Tracking Number:
R41AI100428
Solicitation Year:
2012
Solicitation Topic Code:
NIAID
Solicitation Number:
PA10-124
Small Business Information
7 GAY DR, GREAT NECK, NY, -
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
829942437
Principal Investigator:
ECKARD WIMMER
(516) 689-6000
ewimmer@ms.cc.sunysb.edu
Business Contact:
STEFFEN MUELLER
(516) 567-5888
mueller@codagenix.com
Research Institute:
STATE UNIVERSITY NEW YORK STONY BROOK

STONY BROOK UNIVERSITY
The Office of Sponsered Programs Melville Library Room 5501W
STONY BROOK, NY, 11794-
() -
Nonprofit college or university
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.

* information listed above is at the time of submission.

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