title: Immunogenicity and protective efficacy of recombinant Modified Vaccinia virus Ankara candidate vaccines delivering West Nile virus envelope antigens.
abstract: West Nile virus (WNV) cycles between insects and wild birds, and is transmitted via mosquito vectors to horses and humans, potentially causing severe neuroinvasive disease. Modified Vaccinia virus Ankara (MVA) is an advanced viral vector for developing new recombinant vaccines against infectious diseases and cancer. Here, we generated and evaluated recombinant MVA candidate vaccines that deliver WNV envelope (E) antigens and fulfil all the requirements to proceed to clinical testing in humans. Infections of human and equine cell cultures with recombinant MVA demonstrated efficient synthesis and secretion of WNV envelope proteins in mammalian cells non-permissive for MVA replication. Prime-boost immunizations in BALB/c mice readily induced circulating serum antibodies binding to recombinant WNV E protein and neutralizing WNV in tissue culture infections. Vaccinations in HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice elicited WNV E-specific CD8+ T cell responses. Moreover, the MVA-WNV candidate vaccines protected C57BL/6 mice against lineage 1 and lineage 2 WNV infection and induced heterologous neutralizing antibodies. Thus, further studies are warranted to evaluate these recombinant MVA-WNV vaccines in other preclinical models and use them as candidate vaccine in humans.
authors.affiliation: German Centre for Infection Research (DZIF), Institute for Infectious Diseases and Zoonoses, LMU University of Munich, Veterinaerstrasse 13, D-80539 Munich, Germany.
authors.forename: Asisa
authors.initials: A
authors.lastname: Volz
authors.affiliation: Viroscience Lab, Erasmus Medical Center, Rotterdam, The Netherlands; Artemis One Health Research Institute, Utrecht, The Netherlands.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lim
authors.affiliation: German Centre for Infection Research (DZIF), Institute for Infectious Diseases and Zoonoses, LMU University of Munich, Veterinaerstrasse 13, D-80539 Munich, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Kaserer
authors.affiliation: German Centre for Infection Research (DZIF), Institute for Infectious Diseases and Zoonoses, LMU University of Munich, Veterinaerstrasse 13, D-80539 Munich, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Lülf
authors.affiliation: German Centre for Infection Research (DZIF), Institute for Infectious Diseases and Zoonoses, LMU University of Munich, Veterinaerstrasse 13, D-80539 Munich, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Marr
authors.affiliation: German Centre for Infection Research (DZIF), Institute for Infectious Diseases and Zoonoses, LMU University of Munich, Veterinaerstrasse 13, D-80539 Munich, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Jany
authors.affiliation: Institute for Animal Physiology, LMU University of Munich, Munich, Germany.
authors.forename: Cornelia A
authors.initials: CA
authors.lastname: Deeg
authors.affiliation: Laboratory of Virology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Gorben P
authors.initials: GP
authors.lastname: Pijlman
authors.affiliation: Viroscience Lab, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Penelope
authors.initials: P
authors.lastname: Koraka
authors.affiliation: Viroscience Lab, Erasmus Medical Center, Rotterdam, The Netherlands; Artemis One Health Research Institute, Utrecht, The Netherlands.
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.affiliation: Viroscience Lab, Erasmus Medical Center, Rotterdam, The Netherlands; Artemis One Health Research Institute, Utrecht, The Netherlands.
authors.forename: Byron E
authors.initials: BE
authors.lastname: Martina
authors.affiliation: German Centre for Infection Research (DZIF), Institute for Infectious Diseases and Zoonoses, LMU University of Munich, Veterinaerstrasse 13, D-80539 Munich, Germany. Electronic address: gerd.sutter@lmu.de.
authors.forename: Gerd
authors.initials: G
authors.lastname: Sutter
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D005260:Female; D006736:Horses; D006801:Humans; D056724:Immunity, Humoral; D007117:Immunization, Secondary; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus; D014759:Viral Envelope Proteins / Q000276:immunology*; D019562:Viral Load; D014901:West Nile Fever / Q000517:prevention & control*; D053060:West Nile Virus Vaccines / Q000276:immunology*; D014902:West Nile virus
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D053060:West Nile Virus Vaccines
keywords: Flavivirus; Poxvirus vector; Viral vaccine; West Nile fever