This request for funding for applied research into rapid response vaccines and therapies for MDR-TB is a partnership between the Infectious Disease Research Institute [a not-for-profit research organization], The Vaccine Research Center, NIAID, NIH, and the TB Vaccine Testing and Research Materials Contract at Colorado State University [an academic institution]. Some Mtb antigens have shown promise in animal or in vitro systems, but have not advanced due to either lack of or poor human data. One reason is the paucity of effective adjuvants, which are molecules or compounds that stimulate specific, protective immune responses when combined with antigen. Most adjuvants are in the hands of large pharmaceutical companies. A new generation of vaccines is being developed with these adjuvants but the cost is high. Through component licensing and development of simple formulations, we will provide to the public sector safe, highly effective, low-cost alternatives to adjuvants produced by """"""""big pharma"""""""". We will coordinate activities with the TB Vaccine Testing Contract [NIH, MAID N01-AI-40091] to prioritize Mtb antigen candidates that could benefit from IDRI's adjuvants. We will seek adjuvant rights from patent holders (Intercell, Coley Pharmaceuticals, 3M pharma division, Dainippon Sumitomo Pharmaceuticals) as needed. We have a proprietary patent position on the adjuvant use of glucopyranosil lipid adjuvant ([GLA]; an MPL analogue [Monophosphoryl Lipid A, referred to as MPL]). Our industrial experience will enable us to develop a new generation of effective adjuvant formulations designed to induce the optimal immune response. Development work will emphasize extensive characterization of safety, immune responses and protection in mice, guinea pigs and non-human primates, development of processes that can be transferred and that use materials of non-animal origin, and manufacture/release of adjuvant formulations for clinical testing with priority Mtb antigens. The selection process will emphasis both pre- and post-infection immunization as criteria for prioritization. The selected adjuvant candidate will be subjected to process development, potency and stability assays. By the end of the funding period, we will have defined and developed a new generation adjuvant, collected data for MDR-TB, and evaluated safety of the adjuvant with a GLP toxicology study. We will ensure availability of potent, highly effective adjuvants to facilitate the development of not only effective biodefense vaccines against a category C agent, MDR-TB, but also for the use of the public research sector. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01AI078054-01
Application #
7454641
Study Section
Special Emphasis Panel (ZAI1-TP-M (J2))
Program Officer
Lacourciere, Karen A
Project Start
2008-05-01
Project End
2012-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
1
Fiscal Year
2008
Total Cost
$979,306
Indirect Cost
Name
Infectious Disease Research Institute
Department
Type
DUNS #
809846819
City
Seattle
State
WA
Country
United States
Zip Code
98102
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