IDENTIFICATION OF AN IMMUNE CORRELATE OF PROTECTION FOR DENGUE

Abstract

A correlate of protection has been defined as a "laboratory result. . that has an accepted positive correlation with the induction by a vaccine of a protective immune response in vaccines" (Markoff 2000). In human clinical trials designed to prove efficacy of a vaccine, one of the goals is to identify the protective immune response that is correlated to clinical protection from disease (Plotkin 2008). Although considerable research has been conducted on the immune response to dengue virus infection, an immune correlate of protection has not been clearly defined. The identification and acceptance of an immune correlate of protection would not only provide a more rapid means of evaluating new dengue vaccines, but would also reduce the size of human clinical studies necessary to prove efficacy of a new vaccine, and very likely decrease the time required to obtain a licensed vaccine. The aims of this proposal include: 1) identification of the LD50 for each of the four dengue strains selected for this research in the AG129 mouse model, 2) establishing whether neutralizing antibody titer is correlated with protection from viremia and mortality following passive transfer of polyclonal antibodies, and 3) using human polyclonal antibodies collected under a minimal risk protocol, compare the protection from viremia and mortality afforded by the human antibodies with that of the mouse polyclonal antibodies to determine whether antibody protection of each are correlated in the mouse model.