title: A live attenuated vaccine for Lassa fever made by reassortment of Lassa and Mopeia viruses.
abstract: Lassa virus (LASV) and Mopeia virus (MOPV) are closely related Old World arenaviruses that can exchange genomic segments (reassort) during coinfection. Clone ML29, selected from a library of MOPV/LASV (MOP/LAS) reassortants, encodes the major antigens (nucleocapsid and glycoprotein) of LASV and the RNA polymerase and zinc-binding protein of MOPV. Replication of ML29 was attenuated in guinea pigs and nonhuman primates. In murine adoptive-transfer experiments, as little as 150 PFU of ML29 induced protective cell-mediated immunity. All strain 13 guinea pigs vaccinated with clone ML29 survived at least 70 days after LASV challenge without either disease signs or histological lesions. Rhesus macaques inoculated with clone ML29 developed primary virus-specific T cells capable of secreting gamma interferon in response to homologous MOP/LAS and heterologous MOPV and lymphocytic choriomeningitis virus. Detailed examination of two rhesus macaques infected with this MOPV/LAS reassortant revealed no histological lesions or disease signs. Thus, ML29 is a promising attenuated vaccine candidate for Lassa fever.
authors.affiliation: Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore, MD 21201, USA. lukashev@umbi.umd.edu
authors.forename: Igor S
authors.initials: IS
authors.lastname: Lukashevich
authors.forename: Jean
authors.initials: J
authors.lastname: Patterson
authors.forename: Ricardo
authors.initials: R
authors.lastname: Carrion
authors.forename: Dmitry
authors.initials: D
authors.lastname: Moshkoff
authors.forename: Anysha
authors.initials: A
authors.lastname: Ticer
authors.forename: Juan
authors.initials: J
authors.lastname: Zapata
authors.forename: Kathleen
authors.initials: K
authors.lastname: Brasky
authors.forename: Robert
authors.initials: R
authors.lastname: Geiger
authors.forename: Gene B
authors.initials: GB
authors.lastname: Hubbard
authors.forename: Joseph
authors.initials: J
authors.lastname: Bryant
authors.forename: Maria S
authors.initials: MS
authors.lastname: Salvato
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007835:Lassa Fever / Q000276:immunology* / Q000473:pathology; D007836:Lassa virus / Q000235:genetics / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000821:virology; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008808:Mice, Inbred CBA; D012367:RNA, Viral / Q000235:genetics; D013154:Spleen / Q000276:immunology; D014613:Vaccines, Attenuated; D019562:Viral Load; D014765:Viral Vaccines
chemical_list: D012367:RNA, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines