NEONATAL VACCINE ADJUVANT POTENTIAL OF TOLL-LIKE RECEPTOR 8 AGONISTS

Harvard Medical School, Boston MA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human newborns are functionally immunodeficient and often mount poor memory responses, frustrating efforts to immunize this susceptible population. There is thus an unmet medical need for more effective neonatal vaccine adjuvants. Toll-like receptor (TLR) agonists are potential vaccine adjuvants, but human neonatal cord blood monocytes show impaired TLR-mediated production of Th1-polarizing cytokines in response to agonists of TLRs 1-7, reflecting the inhibitory effect of high cellular cAMP levels in neonatal cells (Levy J Immunol 2006). In marked contrast, TLR8 agonists are uniquely capable of activating TNF- and IL-12 production from neonatal monocytes (Levy Blood 2006), suggesting potential efficacy as neonatal vaccine adjuvants.