y / Abstract Vectored immunoprophylaxis, or antibody gene transfer for infectious disease, is a promising new strategy to provide protection against high risk infectious agents, supplementing vaccine and passive immunization efforts. It has been demonstrated to be effective against HIV and Dengue virus in animal models, and there is currently an ongoing human trial for HIV prevention in high-risk individuals with an adeno-associated viral vector (AAV) delivering the gene for a broadly neutralizing HIV antibody. We propose to expand these efforts to the filoviruses, starting with the Ebolavirus Zaire (EBOV). EBOV causes severe hemorrhagic fever, with a high mortality between 30 and 90%, depending on the virus. Although the recent EBOV epidemic appears to be waning, the outbreak was classified by the WHO as an international public health emergency. In addition, Ebolavirus is a potential bioterrorism agent (Category A). While recent reports suggest optimism for an Ebola vaccine, these are early trials with much work to be done to prove efficacy, and to characterize the onset of protection and durability. Passive immunization has shown great promise against EBOV in a therapeutic setting, however, production capabilities are not yet available for protection of a large segment of the population, and passive immunization requires repeated administration if used in a prophylactic setting. As such, there is an ongoing need for increasing the repertoire of immunoprotectants such as vectored antibodies.
We will use mAb 4G7 gene transfer to compare the expression patterns from both AAV and plasmid based systems, and to assess efficacy in a live virus challenge model in mice compared to the native murine 4G7 mAb. The results will provide the basis for a definitive investigation during which time the plasmid and AAV approaches will be evaluated head-to head and in combination in non-human primates.
