DNA vaccine initiates replication of live attenuated chikungunya virus in vitro and elicits protective immune response in mice

Irina Tretyakova, Jason Hearn, Eryu Wang, Scott Weaver, Peter Pushko

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1882-1890
Number of pages9
JournalJournal of Infectious Diseases
Volume209
Issue number12
DOIs
StatePublished - Jun 15 2014

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Chikungunya virus
DNA Vaccines
Immunization
Vaccines
DNA
Vaccination
Plasmids
Clone Cells
Attenuated Vaccines
In Vitro Techniques
Pandemics
Virus Replication
Neutralizing Antibodies
Disease Outbreaks
Transfection
Cultured Cells
Genome
Viruses
Technology

Keywords

  • alphavirus
  • Chikungunya fever
  • Chikungunya virus
  • CHIKV
  • DNA vaccine
  • live attenuated vaccine

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

DNA vaccine initiates replication of live attenuated chikungunya virus in vitro and elicits protective immune response in mice. / Tretyakova, Irina; Hearn, Jason; Wang, Eryu; Weaver, Scott; Pushko, Peter.

In: Journal of Infectious Diseases, Vol. 209, No. 12, 15.06.2014, p. 1882-1890.

Research output: Contribution to journalArticle

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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.",
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