Grant: Op. Grant: Innovative Ebola Research: Transmission, spread, containment, prevent

Ebola are among the most deadly infectious agents known to man, causing severe hemorrhagic fever in humans and nonhuman primates with fatality rates as high as 90%. Currently there are no licensed vaccines or treatments that prevent or cure infection with Ebola virus, however, monoclonal antibody (MAb)-based therapies have been shown to be efficient at reversing the progression of a lethal Ebola virus infection in nonhuman primates. These studies demonstrate that the antibody mediated immune response correlates with survival and plays an important role in protection. Production of MAbs for use in humans, however, is costly and labor-intensive and immunity does not last long. One way to get around the problems associated with passively immunizing people is to use the body to "manufacture" neutralizing MAbs, by employing a method called vectored immunoprophylaxis (VIP). VIP involves a single injection into the muscle of an adeno-associated virus (AAV) vector expressing genes encoding pathogen specific broadly neutralizing MAbs leading to continuous and sustained secretion of antibodies into the blood stream and protection against infection. VIP has been shown to be very effective at protecting mice against infection with HIV as well as protecting rhesus macaques against infection with simian immunodeficiency virus. Moreover, AAV vectors have been widely used in humans and have a proven safety record. Given that cocktails of MAbs are effective at preventing illness and death in nonhuman primates infected with Ebola virus, VIP antibody gene transfer could be used for pre-exposure prevention in an Ebola virus outbreak. The goal of this project is to construct AAV vectors expressing neutralizing antibody genes against Ebola virus (MAbs) and to compare the efficacy of VIP against Ebola virus infection in nonhuman primates to that of plasmid DNA or free MAbs.