C5a Agonist as a Vaccine Adjuvant for the Aged

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DESCRIPTION (provided by applicant): A major cause of death in the elderly is infectious disease, due in great measure to the age related loss of immune vigor. The ability to mount a strong immune response declines greatly with age. This is an important factor in the sub-optimal level of protection provided by vaccine to the elderly. The ultimate goal of this research program is to develop a vaccine adjuvant that is effective in the elderly population, using an agonist of the complement C5a receptor as a novel molecular adjuvant. This C5a agonist preferentially binds to the C5a receptor on antigen presenting cells but not to the C5a receptor on inflammatory polymorphonuclear cells. When directly coupled to antigenic epitopes, this C5a agonist peptide can induce Ag-specific CTLs in addition to humoral responses. It targets antigen directly to dendritic cells and enhances the early activation of T lymphocytes from both young and aged mice. Using a well-established mouse model of aging, the first specific aim will identify the specific receptor(s) bound by the C5a agonist. The second aim will examine the immediate biological consequences of activation via the C5a receptor, and the third aim will examine the in vivo response to a C5a agonist-protein conjugate vaccine.