title: Chikungunya virus host range E2 transmembrane deletion mutants induce protective immunity against challenge in C57BL/6J mice.
abstract: A vaccine against Chikungunya virus (ChikV), a reemerging pathogenic arbovirus, has been made by attenuating wild-type (WT) virus via truncation of the transmembrane domain (TMD) of E2 and selecting for host range (HR) mutants. Mice are a standard model system for ChikV disease and display the same symptoms of the disease seen in humans. Groups of mice were inoculated with one of three ChikV HR mutants to determine the ability of each mutant strain to elicit neutralizing antibody and protective immunity upon virus challenge. One mutant, ChikV TM17-2, fulfilled the criteria for a good vaccine candidate. It displayed no reactogenicity at the site of injection, no tissue disease in the foot/ankle and quadriceps, and no evidence of viral persistence in foot/ankle tissues 21 days after infection. Upon challenge with a highly pathogenic strain of ChikV, the mutant blocked viral replication in all tissues tested. This study identified a ChikV HR mutant that grows to high levels in insect cells but was restricted in the ability to assemble virus in mammalian cells in vitro. The study demonstrates that these HR strains are attenuated in the mammalian host and warrant further development as live-attenuated vaccine strains.
authors.affiliation: Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, North Carolina, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Piper
authors.forename: Mariana
authors.initials: M
authors.lastname: Ribeiro
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Smith
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Briggs
authors.forename: Emerson
authors.initials: E
authors.lastname: Huitt
authors.forename: Kavita
authors.initials: K
authors.lastname: Nanda
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Spears
authors.forename: Michelle
authors.initials: M
authors.lastname: Quiles
authors.forename: John
authors.initials: J
authors.lastname: Cullen
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Thomas
authors.forename: Dennis T
authors.initials: DT
authors.lastname: Brown
authors.forename: Raquel
authors.initials: R
authors.lastname: Hernandez
mesh_terms: D018354:Alphavirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D002460:Cell Line; D065632:Chikungunya Fever; D002646:Chikungunya virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology; D058507:Host Specificity; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D017384:Sequence Deletion; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines
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