Zalgen Labs — Department of Health and Human Services SBIR Phase I: NIAID

Description

DESCRIPTION provided by applicant Several arenaviruses chiefly Lassa virus LASV in West Africa and Jun n virus JUNV in the Pampas region of Argentina cause hemorrhagic fever HF disease in humans and pose a serious public health concern in their endemic regions Thus LASV is estimated to infect several hundred thousand individuals yearly in its endemic regions of West Africa resulting in a high number of Lassa fever LF cases associated with high morbidity and mortality Likewise JUNV causes Argentine HF AHF a disease associated with hemorrhagic and neurological manifestations and fatality rates of On the other hand although the worldwide distributed prototypic arenavirus lymphocytic choriomeningitis virus LCMV does not cause HF evidence indicates that LCMV is a neglected important human pathogen Thus LCMV has been shown to cause a significant number of cases of congenital neurological and ophthalmological diseases Moreover LCMV poses a serious threat to immunocompromised individuals as tragically documented recently by fatal cases of LCMV infection associated with patients undergoing transplant procedures In addition epidemiological studies have shown a high seroprevalence of LCMV in the United States and other populations tested raising the question of whether LCMV may contribute to the many cases of undiagnosed aseptic meningitis reported yearly Besides a public health risk LCMV poses also a credible biodefense threat and is classified as a Category A priority pathogen by the NIAID Public health concerns posed by LCMV infection of humans are aggravated by the lack of Food and Drug Administration FDA licensed vaccines and current anti arenaviral therapy being limited to the off label use of ribavirin which is only partially effective and associated with side effects The significance of LCMV in human health and biodefense readiness together with the limited existing armamentarium to combat LCMV infections highlight the importance of developing therapies to treat human LCMV infections resulted from an accidental virus exposure a potential intentional virus release and or LCMV infections of immunocompromised individuals To this end we propose to combine the use of our state of the art LCMV reverse genetics with the access to a unique collection of LASV glycoprotein GP specific human monoclonal antibodies hMAbs derived from different LF survivors to identify and characterize hMAbs with broadly neutralizing activity BNhMAbs in vivo against GPs of different isolates related to human cases of LCMV induced disease PUBLIC HEALTH RELEVANCE The worldwide distributed prototypic arenavirus lymphocytic choriomeningitis virus LCMV does not cause hemorrhagic fever but evidence indicates that LCMV is a neglected important human pathogen LCMV has been shown to cause a significant number of cases of congenital neurological and ophthalmological diseases Moreover LCMV poses a serious threat to immunocompromised individuals as tragically documented recently by fatal cases of LCMV infection associated with patients undergoing transplant procedures Epidemiological studies have shown a high seroprevalence of LCMV in the United States and other populations tested raising the question of whether LCMV may contribute to the many cases of undiagnosed aseptic meningitis reported yearly To this end we propose characterize a unique collection of greater than Lassa virus LASV a pathogenic arenavirus in humans and the causative agent of Lassa fever glycoprotein GP specific human monoclonal antibodies hMAbs derived from different Lassa fever survivors to identify and characterize hMAbs with broadly neutralizing activity BNhMAbs in vivo against GPs of different isolates related to human cases of LCMV induced disease