This response to RFA 05-019 is from the Mycobacteria Research Laboratories at Colorado State University, the Infectious Disease Research Institute in Seattle, and Mycos Research, Loveland, Colorado. The purpose of this application has an applied scientific basis and consists of prioritization of new promising drugs, as well as mycobacterial antigens that have promise as post-exposure vaccines, to deal with a deliberate exposure of individuals to an isolate of Mycobacterium tuberculosis, a Class C pathogen, that might potentially be resistant to all known conventionally used TB drugs. Several promising lead compounds as well new investigational drugs such as PA-824 have recently been tested at CSU and will be explored further in this program against MDR strains. In addition, three leading pharmaceutical companies have all expressed their willingness to collaborate in this program and to provide additional compounds already known to be active against drug sensitive M. tuberculosis. In parallel studies we will also lend our proven expertise in TB vaccine research to deal with the more difficult issue of developing a rapidly active post-exposure vaccine, based upon early results detailed in this proposal indicating that this can be achieved. These are protein based, and in addition we will test a new generation of adjuvants selected for potent TH1 responses. Once new candidates are identified they will be tested in conjunction with new chemotherapy regimens based upon our results. Safety testing issues, toxicology testing, and process development leading to GMP production are also planned for the later stages of this proposed program. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI070456-02
Application #
7276755
Study Section
Special Emphasis Panel (ZAI1-LR-M (M1))
Program Officer
Lacourciere, Karen A
Project Start
2006-08-15
Project End
2011-07-31
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
2
Fiscal Year
2007
Total Cost
$1,213,289
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Microbiology/Immun/Virology
Type
Schools of Veterinary Medicine
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
Shanley, Crystal A; Ireton, Gregory C; Baldwin, Susan L et al. (2014) Therapeutic vaccination against relevant high virulence clinical isolates of Mycobacterium tuberculosis. Tuberculosis (Edinb) 94:140-7
Ackart, David F; Hascall-Dove, Laurel; Caceres, Silvia M et al. (2014) Expression of antimicrobial drug tolerance by attached communities of Mycobacterium tuberculosis. Pathog Dis 70:359-69
Orme, Ian M (2014) A new unifying theory of the pathogenesis of tuberculosis. Tuberculosis (Edinb) 94:8-14
Shanley, Crystal A; Streicher, Elizma M; Warren, Robin M et al. (2013) Characterization of W-Beijing isolates of Mycobacterium tuberculosis from the Western Cape. Vaccine 31:5934-9
Orme, Ian M (2013) Vaccine development for tuberculosis: current progress. Drugs 73:1015-24
Palanisamy, Gopinath S; Kirk, Natalie M; Ackart, David F et al. (2012) Uptake and accumulation of oxidized low-density lipoprotein during Mycobacterium tuberculosis infection in guinea pigs. PLoS One 7:e34148
Henao-Tamayo, Marcela; Obregón-Henao, Andrés; Ordway, Diane J et al. (2012) A mouse model of tuberculosis reinfection. Tuberculosis (Edinb) 92:211-7
Shang, Shaobin; Shanley, Crystal A; Caraway, Megan L et al. (2012) Drug treatment combined with BCG vaccination reduces disease reactivation in guinea pigs infected with Mycobacterium tuberculosis. Vaccine 30:1572-82
Kato-Maeda, Midori; Shanley, Crystal A; Ackart, David et al. (2012) Beijing sublineages of Mycobacterium tuberculosis differ in pathogenicity in the guinea pig. Clin Vaccine Immunol 19:1227-37
Palanisamy, Gopinath S; Kirk, Natalie M; Ackart, David F et al. (2011) Evidence for oxidative stress and defective antioxidant response in guinea pigs with tuberculosis. PLoS One 6:e26254

Showing the most recent 10 out of 25 publications