Chikungunya virus host range E2 transmembrane deletion mutants induce protective immunity against challenge in C57BL/6J mice
Autor(es): Piper Amanda, Ribeiro Mariana, Smith Katherine M, Briggs Caitlin M, Huitt Emerson, Nanda Kavita, Spears Carla J, Quiles Michelle, Cullen John, Thomas Malcolm E, Brown Dennis T, Hernandez Raquel
Resumo: 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 - selecting for host range (HR) mutants. Mice are a st-ard model system for ChikV disease - 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 - protective immunity upon virus challenge. One mutant, ChikV TM17-2, fulfilled the criteria for a good vaccine c-idate. It displayed no reactogenicity at the site of injection, no tissue disease in the foot/ankle - quadriceps, - 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 - warrant further development as live-attenuated vaccine strains.
Imprenta: Journal of Virology, v. 87, n. 12, p. 6748-6757, 2013
Identificador do objeto digital: 10.1128/JVI.03357-12
Descritores: Chikungunya virus - Arbovirus ; Chikungunya virus - Biochemistry ; Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Immunology
Data de publicação: 2013
