title: Machupo Virus Expressing GPC of the Candid#1 Vaccine Strain of Junin Virus Is Highly Attenuated and Immunogenic.
abstract: Machupo virus (MACV) is the causative agent of Bolivian hemorrhagic fever. Our previous study demonstrated that a MACV strain with a single amino acid substitution (F438I) in the transmembrane domain of glycoprotein is attenuated but genetically unstable in mice. MACV is closely related to Junin virus (JUNV), the causative agent of Argentine hemorrhagic fever. Others and our group have identified the glycoprotein to be the major viral factor determining JUNV attenuation. In this study, we tested the compatibility of the glycoprotein of the Candid#1 live-attenuated vaccine strain of JUNV in MACV replication and its ability to attenuate MACV in vivo. Recombinant MACV with the Candid#1 glycoprotein (rMACV/Cd#1-GPC) exhibited growth properties similar to those of Candid#1 and was genetically stable in vitro. In a mouse model of lethal infection, rMACV/Cd#1-GPC was fully attenuated, more immunogenic than Candid#1, and fully protective against MACV infection. Therefore, the MACV strain expressing the glycoprotein of Candid#1 is safe, genetically stable, and highly protective against MACV infection in a mouse model.
  
  
  OBJECTIVE
  Currently, there are no FDA-approved vaccines and/or treatments for Bolivian hemorrhagic fever, which is a fatal human disease caused by MACV. The development of antiviral strategies to combat viral hemorrhagic fevers, including Bolivian hemorrhagic fever, is one of the top priorities of the Implementation Plan of the U.S. Department of Health and Human Services Public Health Emergency Medical Countermeasures Enterprise. Here, we demonstrate for the first time that MACV expressing glycoprotein of Candid#1 is a safe, genetically stable, highly immunogenic, and protective vaccine candidate against Bolivian hemorrhagic fever.
authors.affiliation: Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Koma
authors.affiliation: Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Patterson
authors.affiliation: Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Seregin
authors.affiliation: Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
authors.forename: Payal D
authors.initials: PD
authors.lastname: Maharaj
authors.affiliation: Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
authors.forename: Milagros
authors.initials: M
authors.lastname: Miller
authors.affiliation: Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
authors.forename: Jeanon N
authors.initials: JN
authors.lastname: Smith
authors.affiliation: Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
authors.forename: Aida G
authors.initials: AG
authors.lastname: Walker
authors.affiliation: Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Hallam
authors.affiliation: Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA slpaessl@utmb.edu.
authors.forename: Slobodan
authors.initials: S
authors.lastname: Paessler
mesh_terms: D000825:Animal Structures / Q000473:pathology; D000818:Animals; D006477:Arenaviruses, New World / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D001835:Body Weight; D004195:Disease Models, Animal; D042822:Genomic Instability; D006478:Hemorrhagic Fever, American / Q000473:pathology / Q000517:prevention & control; D006651:Histocytochemistry; D008562:Membrane Glycoproteins / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D016019:Survival Analysis; D013696:Temperature; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics*; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D014774:Virulence
chemical_list: C555941:GPC protein, junin virus; D008562:Membrane Glycoproteins; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; D014765:Viral Vaccines