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Newborn babies can't be immunized against most diseases, because they are unable to mount effective immune responses to the vaccines, leaving them at high risk for infections. Ofer Levy, MD, PhD, in the Division of Infectious Diseases, wants to change that. "Worldwide, there are more than 2 million deaths a year from infection in children less than 6 months of age," he says. "Also, from a global health perspective, if you can give a vaccine at birth, a much higher percentage of the population can be covered."
The body's first line of defense against infection is a group of receptors on the surface of certain white blood cells, known as toll-like receptors (TLRs). In newborns, most TLRs respond poorly to stimulation, but Levy's team discovered that one type—TLR8 -- triggers a robust immune response equal to that of adults. Levy now wants to develop TLR8 stimulators, or agonists, as a vaccine adjuvant to shore up newborns' immune defenses.
In May, Levy received a $100,000 grant from the Bill & Melinda Gates Foundation, part of a global health initiative. His team, led at the bench by Victoria Philbin, PhD, has shown that TLR8 agonists induce robust immune responses in both newborn humans and monkeys when tested on white blood cells in the laboratory. By taking weekly blood samples from monkeys over time, they've also verified that the heightened immune response isn't limited to newborns. "We've demonstrated that TLR8 agonists maintain their advantage during the whole phase of susceptibility to infection," says Levy.
Levy now plans to take the research to live monkeys, testing vaccine antigens with and without a TLR8 agonist. "We'll ask whether in the presence of TLR8 we see a stronger immune response, more antibody formation, faster antibody formation and generation of memory lymphocytes," he says. A range of TLR8 agonists are in development by biopharmaceutical companies, and Levy's ultimate goal is to test their safety in humans.
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