Developing Vaccine Candidates for the SARS Coronavirus
Project Number5P01AI059443-04
Contact PI/Project LeaderBARIC, RALPH S
Awardee OrganizationUNIV OF NORTH CAROLINA CHAPEL HILL
Description
Abstract Text
DESCRIPTION (provided by applicant): The overall goals of the proposed Program Project are to identify the genetic determinants of SARS-CoV pathogenesis and virulence, and develop candidate live attenuated, killed, and recombinant virus vaccines that protect animal models from wild type virus challenge. The Program is based on extensive preliminary studies by an existing team with considerable expertise in coronavirus molecular genetics and replication, viral pathogenesis and vaccine design. Two overall hypotheses are central to the Program Project, both based on extensive molecular genetic and immunologic studies on coronavirus. We hypothesize that mutagenic inactivation of various genes and functional domains will reveal the molecular determinants of SARS pathogenesis and virulence following introduction of recombinant viruses into small animal models. These studies will allow for concurrent development of live attenuated viruses that could be used directly as vaccines, or as seed stocks for developing safer "killed" vaccines. This hypothesis is supported in the preliminary empirical studies demonstrating that specific mutations and genetic deletions can be introduced into the SARS-CoV genome and the successful rescue of viable viruses. Our second hypothesis is that existing virus vaccine platforms, either alone or in combination, will induce strong protective immune responses against the SARS-CoV. Thus, we anticipate that the project will 1) rapidly identify genetic determinants of SARS-CoV pathogenesis and virulence; 2) produce a number of attenuated SARS viruses that serve as seed stocks for safer candidate live or killed vaccines and recombinant vaccines; 3) evaluate the efficacy of early vaccine candidates in animals; and 4) select the best of these for further evaluation. Concordant with these pathogenesis and vaccine studies, the program uses SARS-CoV as a model to attack fundamental issues regarding the safety of live attenuated viruses that are germane to many important RNA and DNA viruses. Consequently, the program addresses a number of basic questions that are germane to elucidating the molecular mechanisms governing the evolution and the emergence of new coronaviruses in humans. Finally, the program develops a large number of novel reagents that will propel SARS-CoV research forward, including the development of an infectious cDNA, novel recombinant viruses, recombinant proteins, and antiserum directed against the SARS-CoV proteome.
National Institute of Allergy and Infectious Diseases
CFDA Code
855
DUNS Number
608195277
UEI
D3LHU66KBLD5
Project Start Date
01-May-2005
Project End Date
31-January-2010
Budget Start Date
01-February-2008
Budget End Date
31-January-2009
Project Funding Information for 2008
Total Funding
$1,854,836
Direct Costs
$1,471,838
Indirect Costs
$382,998
Year
Funding IC
FY Total Cost by IC
2008
National Institute of Allergy and Infectious Diseases
$1,854,836
Year
Funding IC
FY Total Cost by IC
Sub Projects
No Sub Projects information available for 5P01AI059443-04
Publications
Publications are associated with projects, but cannot be identified with any particular year of the project or fiscal year of funding. This is due to the continuous and cumulative nature of knowledge generation across the life of a project and the sometimes long and variable publishing timeline. Similarly, for multi-component projects, publications are associated with the parent core project and not with individual sub-projects.
No Publications available for 5P01AI059443-04
Patents
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Outcomes
The Project Outcomes shown here are displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed are those of the PI and do not necessarily reflect the views of the National Institutes of Health. NIH has not endorsed the content below.
No Outcomes available for 5P01AI059443-04
Clinical Studies
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History
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Similar Projects
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