NIH Supports Novel Vaccine and Antimicrobial Research at NYU

By Vivien Marx

Evgeny A. Nudler, professor of biochemistry at the School of Medicine, recently received the Director’s Pioneer Award from the National Institutes of Health (NIH). The award provides Nudler with $2.5 million for his research over five years.

“The Pioneer Award supports exceptionally creative scientists who bring their talents, expertise, and perspectives to bear on some of the biggest challenges in biomedical research,” says Elias Zerhouni, director of NIH.

Nudler and the 10 scientists in his lab have worked on several different types of complex biological questions, and found novel answers in each case. As he continues that research as well as his two new ventures, Nudler plans to use the award to apply his expertise in bacteria to create platform solutions for a wide range of biomedical challenges.

“What we have proposed is to create conceptually new types of antimicrobials and vaccines,” says Nudler.

Because neither of these drug classes are a popular area of industrial research and development, academic researchers must fill the gap, he says. While his ongoing work has led to important basic research discoveries, he wants to work on additional projects that can potentially help treat or prevent infections in the not- too-distant future.

With the Pioneer Award, Nudler and his group plan to develop heat-stable vaccines. Vaccines are usually parts of microbes that have been killed or weakened. Vaccines are expensive to make, usually need to be injected, and are difficult to store. For example, they must be kept refrigerated at all times prior to injection, which is often an impossible task in developing countries, says Nudler. Vaccines based on his ideas may not face those challenges.

These new vaccines involve the mucosal immune system. Mucous membranes such as the linings of the gastrointestinal, urogenital, and respiratory tracts are the ports of entry into the body for pathogens such as the flu virus. Although 80 percent of the body’s response to invaders is through the mucosal immune response, most vaccines do not target this very first contact between a pathogen and the host.

“If someone learned how to strengthen this immune response, it could prevent numerous infections,” says Nudler.

The other Pioneer Award project in Nudler’s lab will involve the development of novel types of antimicrobials. In past work he has synthesized tailored chemicals that can react in concert with nitric oxide (NO) to deactivate bacterial enzymes.

Nitric oxide levels are always higher in infected areas of the body because cells of the immune system, such as macrophages, produce NO to combat and kill bacteria. Nudler’s plan is for this novel antimicrobial to tap into the power of NO and amplify it.

Much work remains to be done to develop the right kind of small molecule, says Nudler, but past research in his lab has shown that the concept can work.

“For bacteria, it is very difficult to acquire resistance to these types of chemicals,” he says. The idea is to develop a binary weapon against bacteria. “It will kill bacteria only in the presence of NO.”

The NIH Director’s Pioneer Award, first launched in 2004, supports scientists of exceptional creativity who propose innovative approaches to major challenges in biomedical research. It is a grant for future research that has the potential to produce an unusually high impact on biomedical research. The award is a component of the NIH Roadmap for Medical Research.