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Dr Levy's project is one of 81 grants announced by the Gates Foundation in the second funding round of Grand Challenges Explorations, an initiative to help scientists around the world explore bold and largely unproven ways to improve health in developing countries. The grants were provided to scientists in 17 countries on six continents.

To receive funding, Dr. Levy showed in a two-page application how his idea falls outside current scientific paradigms and might lead to significant advances in global health. The initiative is highly competitive, receiving more than 3,000 proposals in this round.

Newborns are at high risk of infection leading to many cases of disability or death, but most vaccines do not work well when given in the first day of life, thereby frustrating efforts to protect this vulnerable population. Dr. Levy has discovered that certain synthetic molecules (called "imidazoquinolines") that mimic parts of a virus can effectively activate human neonatal white blood cells suggesting these molecules can be used as adjuvants to boost neonatal vaccine responses. The project will build on these discoveries to develop these agents to produce effective neonatal vaccines.

"Newborns are highly susceptible to infection, leading to more than 2 million deaths a year worldwide in children less than 6 months of age," says Levy. "Unfortunately, many vaccines aren't effective at birth, creating a critical need to develop improved vaccination approaches for these kids, whose immune system is distinct from, and less active than that of, adults. Using novel imidazoquinoline molecules to boost neonatal vaccine responses may be an effective and practical solution to protect newborns from life-threatening bacterial and viral pathogens."

The research focuses on how certain immune-activating imidazoquinoline molecules also known as Toll-like receptor 8 (TLR8) agonists activate human newborn cells and in animal models, enhance vaccine responses. Unlike many other immune stimuli that are not effective towards neonatal white blood cells, molecules that activate TLR8 receptors trigger a robust response in newborns.

Understanding the mechanisms by which TLR8 agonists activate human neonatal white blood cells could lead to more effective vaccines that are active at birth, don't require additional doses, and are orally, topically or subcutaneously administered, thereby preventing life-threatening infections in newborns and infants at birth, most children's most reliable point of contact with healthcare providers.

"We're grateful to the Gates Foundation for this generous grant," says Levy. "Our lab is one of only a few in the world conducting research on adjuvant response on newborns. Our cutting-edge approach could create new vaccines to treat a broad range of diseases, including HIV, diarrhea, malaria, pneumonia and tuberculosis for both children and adults worldwide."

"The winners of these grants are doing truly exciting and innovative work," said Dr. Tachi Yamada, president of the Gates Foundation's Global Health Program. "I'm optimistic that some of these exploratory projects will lead to life-saving breakthroughs for people in the world's poorest countries."

Contact:
Amy Sweeney
Children's Hospital Trust
617-355-4102
amy.sweeney@chtrust.org

About Grand Challenges Explorations
Grand Challenges Explorations is a five-year, $100 million initiative of the Gates Foundation to promote innovation in global health. The program uses an agile, streamlined grant process - applications are limited to two pages, and preliminary data are not required. Proposals are reviewed and selected by a committee of foundation staff and external experts, and grant decisions are made within approximately three months of the close of the funding round.

About Ofer Levy, MD, PhD
Research in Dr. Levy's laboratory centers on innate immunity of the human newborn to microbial infection. The overall goal of this work is to identify innate immune pathways as potential targets of immunomodulatory therapies to prevent and treat microbial infection in neonates. In addition to his basic research, Dr. Levy also maintains a strong and active interest in translational research. Levy received his MD and PhD (Microbiology) degrees from New York University. He completed internship, residency, and clinical fellowship training at Children's Hospital Boston and a research fellowship at The Brigham and Women's Hospital.

Children's Hospital Boston, an internationally renowned center for medical research and treatment, is one of the only pediatric hospitals nationwide that focuses on pairing world-class research with clinical resources to develop novel therapies to treat and cure children. Many of the hospital's scientific advancements have far-reaching implications for treating adults, too - they target diseases including prostate and breast cancer, macular degeneration, and Alzheimer's. For more information, visit www.childrenshospital.org