title: DNA vaccine initiates replication of live attenuated chikungunya virus in vitro and elicits protective immune response in mice.
abstract: BACKGROUND
  Chikungunya virus (CHIKV) causes outbreaks of chikungunya fever worldwide and represents an emerging pandemic threat. Vaccine development against CHIKV has proved challenging. Currently there is no approved vaccine or specific therapy for the disease.
  
  
  METHODS
  To develop novel experimental CHIKV vaccine, we used novel immunization DNA (iDNA) infectious clone technology, which combines the advantages of DNA and live attenuated vaccines. Here we describe an iDNA vaccine composed of plasmid DNA that encode the full-length infectious genome of live attenuated CHIKV clone 181/25 downstream from a eukaryotic promoter. The iDNA approach was designed to initiate replication of live vaccine virus from the plasmid in vitro and in vivo.
  
  
  RESULTS
  Experimental CHIKV iDNA vaccines were prepared and evaluated in cultured cells and in mice. Transfection with 10 ng of iDNA was sufficient to initiate replication of vaccine virus in vitro. Vaccination of BALB/c mice with a single 10 μg of CHIKV iDNA plasmid resulted in seroconversion, elicitation of neutralizing antibodies, and protection from experimental challenge with a neurovirulent CHIKV.
  
  
  CONCLUSIONS
  Live attenuated CHIKV 181/25 vaccine can be delivered in vitro and in vivo by using DNA vaccination. The iDNA approach appears to represent a promising vaccination strategy for CHIK and other alphaviral diseases.
authors.affiliation: Medigen, Frederick, Maryland.
authors.forename: Irina
authors.initials: I
authors.lastname: Tretyakova
authors.affiliation: Medigen, Frederick, Maryland.
authors.forename: Jason
authors.initials: J
authors.lastname: Hearn
authors.affiliation: Sealy Center for Vaccine Development and Department of Pathology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Eryu
authors.initials: E
authors.lastname: Wang
authors.affiliation: Sealy Center for Vaccine Development and Department of Pathology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Scott
authors.initials: S
authors.lastname: Weaver
authors.affiliation: Medigen, Frederick, Maryland.
authors.forename: Peter
authors.initials: P
authors.lastname: Pushko
mesh_terms: D018354:Alphavirus Infections / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D065632:Chikungunya Fever; D002646:Chikungunya virus / Q000502:physiology*; D003001:Cloning, Molecular; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004279:DNA, Viral; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D014765:Viral Vaccines
keywords: CHIKV; Chikungunya fever; Chikungunya virus; DNA vaccine; alphavirus; live attenuated vaccine