title: Mice immunized with recombinant vaccinia virus expressing dengue 4 virus structural proteins with or without nonstructural protein NS1 are protected against fatal dengue virus encephalitis.
abstract: We have constructed vaccinia virus recombinants expressing dengue virus proteins from cloned DNA for use in experimental immunoprophylaxis. A recombinant virus containing a 4.0-kilobase DNA sequence that codes for three structural proteins, capsid (C), premembrane (pre-M), and envelope (E), and for nonstructural proteins NS1 and NS2a produced authentic pre-M, E, and NS1 in infected CV-1 cells. Mice immunized with this recombinant were protected against an intracerebral injection of 100 50% lethal doses of dengue 4 virus. A recombinant containing only genes C, pre-M, and E also induced solid resistance to challenge. Deletion of the putative C-terminal hydrophobic anchor of the E glycoprotein did not result in secretion of E from recombinant-virus-infected cells. Recombinants expressing only the E protein preceded by its own predicted N-terminal hydrophobic signal or by the signal of influenza A virus hemagglutinin or by the N-terminal 71 amino acids of the G glycoprotein of respiratory syncytial virus produced glycosylated E protein products of expected molecular sizes. These vaccinia virus recombinants also protected mice.
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
authors.forename: M
authors.initials: M
authors.lastname: Bray
authors.forename: B T
authors.initials: BT
authors.lastname: Zhao
authors.forename: L
authors.initials: L
authors.lastname: Markoff
authors.forename: K H
authors.initials: KH
authors.lastname: Eckels
authors.forename: R M
authors.initials: RM
authors.lastname: Chanock
authors.forename: C J
authors.initials: CJ
authors.lastname: Lai
mesh_terms: D000818:Animals; D002213:Capsid / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D003715:Dengue / Q000517:prevention & control*; D003716:Dengue Virus / Q000276:immunology*; D004660:Encephalitis / Q000517:prevention & control*; D005786:Gene Expression Regulation; D051379:Mice; D011233:Precipitin Tests; D014614:Vaccines, Synthetic; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines
chemical_list: D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D014765:Viral Vaccines