title: Recombinant modified vaccinia virus Ankara expressing glycoprotein E2 of Chikungunya virus protects AG129 mice against lethal challenge.
abstract: Chikungunya virus (CHIKV) infection is characterized by rash, acute high fever, chills, headache, nausea, photophobia, vomiting, and severe polyarthralgia. There is evidence that arthralgia can persist for years and result in long-term discomfort. Neurologic disease with fatal outcome has been documented, although at low incidences. The CHIKV RNA genome encodes five structural proteins (C, E1, E2, E3 and 6K). The E1 spike protein drives the fusion process within the cytoplasm, while the E2 protein is believed to interact with cellular receptors and therefore most probably constitutes the target of neutralizing antibodies. We have constructed recombinant Modified Vaccinia Ankara (MVA) expressing E3E2, 6KE1, or the entire CHIKV envelope polyprotein cassette E3E26KE1. MVA is an appropriate platform because of its demonstrated clinical safety and its suitability for expression of various heterologous proteins. After completing the immunization scheme, animals were challenged with CHIV-S27. Immunization of AG129 mice with MVAs expressing E2 or E3E26KE1 elicited neutralizing antibodies in all animals and provided 100% protection against lethal disease. In contrast, 75% of the animals immunized with 6KE1 were protected against lethal infection. In conclusion, MVA expressing the glycoprotein E2 of CHIKV represents as an immunogenic and effective candidate vaccine against CHIKV infections.
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: van den Doel
authors.affiliation: Institute for Infectious Diseases and Zoonoses, University of Munich LMU, Munich, Germany.
authors.forename: Asisa
authors.initials: A
authors.lastname: Volz
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Jouke M
authors.initials: JM
authors.lastname: Roose
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Varsha D
authors.initials: VD
authors.lastname: Sewbalaksing
authors.affiliation: Laboratory of Virology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Gorben P
authors.initials: GP
authors.lastname: Pijlman
authors.affiliation: Laboratory of Virology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: van Middelkoop
authors.affiliation: Erasmus Medical Center Laboratory Animal Science Center (EDC), Rotterdam, The Netherlands.
authors.forename: Vincent
authors.initials: V
authors.lastname: Duiverman
authors.affiliation: Erasmus Medical Center Laboratory Animal Science Center (EDC), Rotterdam, The Netherlands.
authors.forename: Eva
authors.initials: E
authors.lastname: van de Wetering
authors.affiliation: Institute for Infectious Diseases and Zoonoses, University of Munich LMU, Munich, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Sutter
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands; Artemis One Health, Utrecht, The Netherlands.
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.affiliation: Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands; Artemis One Health, Utrecht, The Netherlands.
authors.forename: Byron E E
authors.initials: BE
authors.lastname: Martina
mesh_terms: D018354:Alphavirus Infections / Q000276:immunology; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D065632:Chikungunya Fever / Q000517:prevention & control*; D002646:Chikungunya virus; D006023:Glycoproteins / Q000276:immunology; D051379:Mice; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006023:Glycoproteins; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines