Development of a Novel Vaccine Vector for Multiple CDC Category A Pathogens; Final rept. 1 Apr 2007-31 Mar 2008

摘要

Specific Aim 1 was to generate a panel of RhCMV/MPV vectors expressing MPV antigens A29L, A35R, M1R and B6R in either the wild type RhCMV vector, or in a vector lacking MHC immunomodulatory genes. To date, two vectors have been constructed and characterized, and we have subsequently selected one WT RhCMV vector (WTRhCMV/A35R) for immunogical characterization in rhesus macaques. Specific Aims 2 and 3 were to establish the pathobiology of WT MPV infection in RMs, and to monitor the immunological consequences of WT MPV infection. To date, eight RMs have been experimentally inoculated intrabronchially with MPV Zaire strain (MPVZ) to define a lethal dose by this route of infection and to characterize the virus/host interactions. Together, completion of these three specific aims will form the foundation for future studies designed to determine the efficacy of the RhCMV/MPV vectors at inducing a protective immune response to MPV challenge in RMs, and to identify viral determinants of pathogenesis.