Development of a Novel Vector for Multiple CDC Category A Pathogens

摘要

The long-term goal of this project is to develop and evaluate human cytomegalovirus (HCMV) as an effective large capacity persistent vaccine vector to provide protective immunity for multiple bioterrorist agents and emerging diseases. The aim of the current proposal was to determine the potential utility of HCMV as vaccine vector for ODO category A agents using rhesus cytomegalovirus (RhCMV) vaccine vectors in combination with the monkeypox (MPV)- rhesus macaque (RM) model. RhCMV is highly homologous to HCMV and the MPV:RM model recapitulates all aspects of smallpox infection of humans. Specific Aim 1 was to generate a panel of RhCMV/MPV vectors expressing MPV antigens A29L A35R Mi Rand B6R in either the wild type RhCMV vector or in a vector lacking MHC immunomodulatory genes. Vectors have been constructed genetically characterized and electroporated into RhCMV permissive cells to reconstitute recombinant viruses. MPV antigen expression of vectors is currently being confirmed. 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 four RMs have been experimentally inoculated intra-bronchially with MPV Zaire strain. Two with 2 x 107 plaque forming units (PFU) and two with 2 x 105 PFU to define a lethal dose by this route of infection and to characterize the virus/host interactions. A summation of the ongoing studies is provided. 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.