Replication competent vaccinia virus (W), the current vaccine for smallpox, can cause severe complications after vaccination, especially in immune suppressed individuals. We are seeking to develop strains of VV that are replication competent, and thus will induce a strong immune response, without the complications associated with vaccination with the current vaccines. Thus, the Aim of this proposal is to prepare conditional mutants of VV that are either dependent on an FDA-approved drug for replication, or are treatable by an FDA-approved drug. For drug-sensitive viruses, individuals who experience complications could be treated with the FDA-approved drug. For drug-dependent viruses, should complications arise, the drug could be withdrawn from vaccinated individuals as a treatment. Drug-dependent viruses have the added advantage that they would not be able to spread in a viable form from vaccinated individuals to contacts. The relative immunogenicity and safety of these two strategies will be compared with that of a current vaccine (Dryvax) in immunocompetent mice (immunogenicity and safety), and in immunodeficient SCID mice (safety only). The most promising of these strains will be engineered into a virus background suitable for use in humans, prepared under GMP conditions and tested in chimpanzees and humans for safety and immunogenicity, compared to Dryvax.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI057303-04
Application #
7086393
Study Section
Special Emphasis Panel (ZAI1-HSD-M (M3))
Program Officer
Challberg, Mark D
Project Start
2003-09-30
Project End
2008-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
4
Fiscal Year
2006
Total Cost
$1,285,455
Indirect Cost
Name
Arizona State University-Tempe Campus
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
943360412
City
Tempe
State
AZ
Country
United States
Zip Code
85287
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Denzler, Karen L; Schriewer, Jill; Parker, Scott et al. (2011) The attenuated NYCBH vaccinia virus deleted for the immune evasion gene, E3L, completely protects mice against heterologous challenge with ectromelia virus. Vaccine 29:9691-6
Denzler, Karen L; Rice, Amanda D; MacNeill, Amy L et al. (2011) The NYCBH vaccinia virus deleted for the innate immune evasion gene, E3L, protects rabbits against lethal challenge by rabbitpox virus. Vaccine 29:7659-69
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