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A vaccine that works in newborns?
Date:3/4/2013

Rx Pharmaceuticals (Seattle, WA), potently stimulate the human immune system and are in clinical trials in patients with certain cancers.

Tested in Levy's lab, one benzazepine, VTX-294, produced a strong immune response in white blood cells from newborns (taken from cord blood samples) as well as whole blood from adults. It induced robust production of cytokines—chemicals that rally the immune response—and proved at least 10 times more potent than the best activator of TLR8 known previously.

"The response was not only equal to that in adults, but VTX 294 was sometimes actually more effective in newborns than adults," notes Levy, the study's senior investigator.

The compound also triggered production of so-called co-stimulatory molecules that enhance immune responses. Moreover, even very low concentrations of VTX-294 strongly activated antigen-presenting cells, a type of white blood cell whose activation induces immune memory—key to effective responses to vaccines.

Toll-like receptors (TLRs), first identified in humans about two decades ago, are part of the innate (rapid) immune response that provides our first defense against infections. Ten types of TLRs are known, and TLR stimulators have begun to be added to vaccines as adjuvants. The main one, monophosphoryl lipid A (MPLA), stimulates TLR4 and is used in the human papillomavirus vaccine Cervarix. However, in a recent clinical trial published in The New England Journal of Medicine, a malaria vaccine with MPLA failed to elicit a sufficient immune response in infants.

With encouraging results in cells from human newborns, Levy and colleagues now hope to formulate VTX 294 or a similar TLR8 stimulator for testing as a vaccine adjuvant in newborn primates, a model in which the lab has expertise, and whose responses to TLR8 closely resemble humans'.

"This one receptor seems to l
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SOURCE Boston Children's Hospital
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