PRE-CLINICAL TESTING OF FILOVIRUS VACCINES IN NONHUMAN PRIMATES

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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. Members of the family Filoviridae cause severe hemorrhagic fevers in humans and nonhuman primates. The most prominent member, Ebola virus, causes outbreaks periodically at 2-10 year intervals since initial identification in 1976. It is a Category A agent and requires manipulation at maximum containment. In the wild, infections initiate from contact of people with dead or dying virus-infected forest animals such as chimpanzees, forest antelope and porcupines that have been regularly found on the rainforest floor in affected areas. The Zaire strain of Ebola is most often associated with outbreaks with very high mortality rates, on average between 80 to 90%. Apart from palliative measures, there is no effective treatment for the disease. To date, no commercial vaccine is available to protect against infection with filoviruses. The immunogenicity of three recombinant subunit proteins of Ebola Zaire virus expressed in an insect cell culture system was previously evaluated in mice. The experiments were successful and led to the selection of vaccine formulations that have further been tested in a live virus challenge experiment (at USAMRlID). Several formulations elicited complete protection against morbidity and mortality caused by the homologous virus strain (Ebola Zaire). Nonhuman ,primates show a similar course of disease upon filovirus infection as humans and are therefore considered to be the model most predictive of human efficacy. After successful demonstration of immunogenicity and efficacy against Ebola Zaire virus in two rodent models (mice and guinea pigs), the leading vaccine candidates therefore have to be evaluated for immunogenicity and protective potential against live virus challenge in non-human primates. If relevant immune responses (antibody and mature lymphocytes) can be demonstrated after immunization with the novel vaccines, this experiment will provide the pivotal proof-of-concept for the technology. Successful completion of this study will validate the efficacy of the Ebola vaccine preparations in advance to the goal of clinical testing.