title: TC83 replicon vectored vaccine provides protection against Junin virus in guinea pigs.
abstract: Junin virus (JUNV) is the etiological agent of the potentially lethal, reemerging human disease, Argentine hemorrhagic fever (AHF). The mechanism of the disease development is not well understood and no antiviral therapy is available. Candid 1, a live-attenuated vaccine, has been developed by the US Army and is being used in the endemic area to prevent AHF. This vaccine is only approved for use in Argentina. In this study we have used the alphavirus-based approach to engineer a replicon system based on a human (United States Food and Drug Administration Investigational New Drug status) vaccine TC83 that express heterologous viral antigens, such as glycoproteins (GPC) of Junin virus (JUNV). Preclinical studies testing the immunogenicity and efficacy of TC83/GPC were performed in guinea pigs. A single dose of the live-attenuated alphavirus based vaccine expressing only GPC was immunogenic and provided partial protection, while a double dose of the same vaccine provided a complete protection against JUNV. This is the first scientific report to our knowledge that the immune response against GPC alone is sufficient to prevent lethal disease against JUNV in an animal model.
authors.affiliation: Galveston National Laboratory, Sealy Vaccine Center and Institute for Human Infections and Immunity, Department of Pathology, University of Texas Medical Branch (UTMB), Galveston, TX 77555-0609, USA.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Seregin
authors.forename: Nadezhda E
authors.initials: NE
authors.lastname: Yun
authors.forename: Allison L
authors.initials: AL
authors.lastname: Poussard
authors.forename: Bi-Hung
authors.initials: BH
authors.lastname: Peng
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Smith
authors.forename: Jeanon N
authors.initials: JN
authors.lastname: Smith
authors.forename: Milagros
authors.initials: M
authors.lastname: Salazar
authors.forename: Slobodan
authors.initials: S
authors.lastname: Paessler
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis; D001117:Arenaviridae Infections / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology; D006168:Guinea Pigs; D018051:Junin virus / Q000235:genetics* / Q000276:immunology*; D009500:Neutralization Tests; D010957:Plasmids / Q000276:immunology; D012093:Replicon / Q000276:immunology*; D016019:Survival Analysis; D013686:Telemetry; D019444:Vaccines, DNA / Q000276:immunology; D014709:Vero Cells; D019562:Viral Load; D010948:Viral Plaque Assay; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D006023:Glycoproteins; D019444:Vaccines, DNA; D014765:Viral Vaccines