title: Single-round infectious particles enhance immunogenicity of a DNA vaccine against West Nile virus.
abstract: DNA vaccines encoding replication-defective viruses are safer than inactivated or live attenuated viruses but may fail to stimulate an immune response sufficient for effective vaccination. We augment the protective capacity of a capsid-deleted flavivirus DNA vaccine by co-expressing the capsid protein from a separate promoter. In transfected cells, the capsid-deleted RNA transcript is replicated and translated to produce secreted virus-like particles lacking the nucleocapsid. This RNA is also packaged with the help of co-expressed capsid protein to form secreted single-round infectious particles (SRIPs) that deliver the RNA into neighboring cells. In SRIP-infected cells, the RNA is replicated again and produces additional virus-like particles, but in the absence of capsid RNA no SRIPs are formed and no further spread occurs. Compared with an otherwise identical construct that does not encode capsid, our vaccine offers better protection to mice after lethal West Nile virus infection. It also elicits virus-neutralizing antibodies in horses. This approach may enable vaccination against pathogenic flaviviruses other than West Nile virus.
authors.affiliation: School of Molecular and Microbial Sciences, University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: Chang
authors.forename: Wen J
authors.initials: WJ
authors.lastname: Liu
authors.forename: Itaru
authors.initials: I
authors.lastname: Anraku
authors.forename: David C
authors.initials: DC
authors.lastname: Clark
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Pollitt
authors.forename: Andreas
authors.initials: A
authors.lastname: Suhrbier
authors.forename: Roy A
authors.initials: RA
authors.lastname: Hall
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Khromykh
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D018177:Flavivirus Infections / Q000235:genetics* / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D051379:Mice; D014162:Transfection / Q000379:methods*; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000235:genetics / Q000627:therapeutic use*; D014771:Virion / Q000235:genetics*
chemical_list: D019444:Vaccines, DNA