title: Marburg virus vaccines based upon alphavirus replicons protect guinea pigs and nonhuman primates.
abstract: Marburg virus (MBGV), for which no vaccines or treatments currently exist, causes an acute hemorrhagic fever with a high mortality rate in humans. We previously showed that immunization with either killed MBGV or a glycoprotein (GP) subunit prevented lethal infection in guinea pigs. In the studies reported here, an RNA replicon, based upon Venezuelan equine encephalitis (VEE) virus, was used as a vaccine vector; the VEE structural genes were replaced by genes for MBGV GP, nucleoprotein (NP), VP40, VP35, VP30, or VP24. Guinea pigs were vaccinated with recombinant VEE replicons (packaged into VEE-like particles), inoculated with MBGV, and evaluated for viremia and survival. Results indicated that either GP or NP were protective antigens while VP35 afforded incomplete protection. As a more definitive test of vaccine efficacy, nonhuman primates (cynomolgus macaques) were inoculated with VEE replicons expressing MBGV GP and/or NP. Three monkeys received packaged control replicons (influenza HA); these died 9 or 10 days after challenge, with typical MBGV disease. MBGV NP afforded incomplete protection, sufficient to prevent death but not disease in two of three macaques. Three monkeys vaccinated with replicons which expressed MBGV GP, and three others vaccinated with both replicons that expressed GP or NP, remained aviremic and were completely protected from disease.
authors.affiliation: United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, Frederick, Maryland, 21702, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hevey
authors.forename: D
authors.initials: D
authors.lastname: Negley
authors.forename: P
authors.initials: P
authors.lastname: Pushko
authors.forename: J
authors.initials: J
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Schmaljohn
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000032:analysis / Q000235:genetics / Q000276:immunology; D002522:Chlorocebus aethiops; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D006168:Guinea Pigs; D008252:Macaca fascicularis; D008379:Marburg Virus Disease / Q000401:mortality / Q000517:prevention & control*; D029024:Marburgvirus / Q000276:immunology*; D009500:Neutralization Tests; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000032:analysis / Q000235:genetics / Q000276:immunology; D016601:RNA-Binding Proteins; D012093:Replicon / Q000235:genetics; D012261:Ribonucleoproteins; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000032:analysis / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*; D014766:Viremia / Q000517:prevention & control
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; C081324:GP-protein, Marburg virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D014765:Viral Vaccines; C073094:nucleoprotein, Marburg virus