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 Synthetic Attenuated 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 the amount 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 been humankind'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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
Project #
5R41AI100428-02
Application #
8490298
Study Section
Special Emphasis Panel (ZRG1-IMM-N (12))
Program Officer
Salomon, Rachelle
Project Start
2012-06-15
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
2
Fiscal Year
2013
Total Cost
$300,000
Indirect Cost
Name
Codagenix, Inc.
Department
Type
DUNS #
829942437
City
Great Neck
State
NY
Country
United States
Zip Code
11024