Government And Industry Team Up To Battle Infectious Diseases

"Infectious diseases such as malaria, tuberculosis and influenza continue to take a devastating toll on people throughout the world," says Anthony S. Fauci, M.D., NIAID director. "Forging partnerships with industry is an important part of NIAID's commitment to research on new ways to prevent and treat these diseases, and to move discoveries quickly from the laboratory to the clinic."

The Challenge Grants are milestone-driven awards, meaning recipients must achieve predetermined product goals during the development process. Progress will be assessed at each milestone and decisions will be made on continuing project funding. Each award will be matched with equal dollars from the recipient company and the combined contributions used to support three-year projects. Programs backed by existing infrastructure and novel design provided the most promise for rapidly producing new drugs or vaccines; these were awarded the grants described below.

**MALARIA**

A $7 million grant to SmithKline Beecham Pharmaceuticals, Collegeville, Pa., will help Pamela French, M.D., M.P.H., D.T.M.H., and colleagues develop a pediatric indication for tafenoquine, a promising new drug already under investigation for preventing malaria in adults. This research will be a collaboration with the U.S. military, led by Colin Ohrt, M.D., M.P.H., of the Walter Reed Army Institute of Research, and also will investigate the ability of tafenoquine to block transmission of the malaria parasite, preventing it from passing from person to person.

Charles Knirsch, M.D., M.P.H., of Pfizer Pharmaceuticals, New York, N.Y., will team with another group of military researchers, led by Walter Reed's Jonathan Berman, M.D., Ph.D., to study azithromycin for treating malaria. To overcome drug resistance, the anti-malaria drugs often are used in combination. A number of these combinations contain drugs that cannot be taken by children or pregnant women. Azithromycin is safe in these groups, however, and the researchers will use a $550,000 grant to help fund a study of this drug in combination with standard anti-malaria agents in Thailand and the Philippines.

**TUBERCULOSIS**

With the aid of a $1.2 million grant to Sequella, Rockville, Md., Marina Protopopova, Ph.D., will direct research on a new generation of antibiotics to battle TB. Her team has identified 300 candidate compounds by screening chemical variants of ethambutol, one of the four first-line drugs recommended for treatment of TB. The researchers will test these second-generation molecules for their efficacy against Mycobacterium tuberculosis so more potent treatment options can be developed.

Researchers from SmithKline Beecham Pharmaceuticals will use a $1.2 million grant to investigate another class of TB drugs by modifying thiolactomycin, a compound that blocks an important metabolic process in certain bacteria and parasites. John Lonsdale, Ph.D., and co-workers will create and test thiolactomycin variants as a new class of anti-TB agent. This drug class should circumvent existing antibiotic resistance mechanisms of bacteria, making it a promising approach to treating multi-drug-resistant (MDR) TB. In addition, because thiolactomycin blocks a biochemical pathway common to many microbes, it may be a promising drug for other diseases such as drug-resistant Staphylococcus and Enterococcus infections, malaria and trypanosomiasis.

The NIAID Challenge Grants also will support research on a TB vaccine. Through a $2.3 million award to Corixa Corporation in Seattle, Wash., Steven Reed, Ph.D., will direct preclinical and clinical testing of new candidate vaccines produced using M. tuberculosis proteins. Corixa scientists will test these proteins in animals for their ability to stimulate an appropriate immune response, and then combine several of these proteins into candidate vaccines for further testing.

**INFLUENZA**

In order to develop a better vaccine for use against future flu pandemics, Aviron, Mountain View, Calif., has been awarded $2.7 million to develop a weakened live influenza virus vaccine and to evaluate new mechanisms of production. Shengqiang Li, D.V.M., will lead a team to develop a vaccine that will be given as a nasal mist instead of a shot, making it a promising option for widespread distribution and use.

By matching a $1.4 million grant from NIAID, Aventis Pasteur, Swiftwater, Pa., will develop a technology that allows the rapid engineering and production of specific influenza viruses. Dennis Trent, Ph.D., and co-workers will use a new DNA-based system to produce influenza vaccine candidates. The scientists hope to produce four new vaccines ready for clinical trials and establish that this system can shorten the response time needed to produce vaccines against pandemic influenza viruses.

Current influenza vaccines are grown in chicken eggs, which may be in short supply during a pandemic. Therefore, alternatives must be developed to protect the world's population. Novavax, Rockville, Md., has been awarded $850,000 to produce several non-egg-grown influenza vaccines. Louis Potash, Ph.D., will lead a team of scientists in developing these vaccines, and the most promising will be prepared for use in future clinical trials.

**DENGUE**

A $1.8 million grant to OraVax, Cambridge, Mass., will help develop a vaccine against dengue viruses. Dr. Thomas Monath and his colleagues will use a proven yellow fever vaccine as the backbone for the new vaccines. By replacing a yellow fever gene with genes from the four dengue serotype viruses, the researchers will produce chimeric candidate vaccines ready for initial clinical trials.

NIAID is a component of the National Institutes of Health (NIH). NIAID supports basic and applied research to prevent, diagnose and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies. ###

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.