Next generation sequencing of DNA-launched Chikungunya vaccine virus

Rachmat Hidajat, Brian Nickols, Naomi Forrester, Irina Tretyakova, Scott Weaver, Peter Pushko

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Chikungunya virus (CHIKV) represents a pandemic threat with no approved vaccine available. Recently, we described a novel vaccination strategy based on iDNA® infectious clone designed to launch a live-attenuated CHIKV vaccine from plasmid DNA in vitro or in vivo. As a proof of concept, we prepared iDNA plasmid pCHIKV-encoding the full-length cDNA of the 181/25 vaccine. The DNA-launched CHIKV-virus was prepared and compared to the 181/25 virus. Illumina HiSeq2000 sequencing revealed that with the exception of the 3' untranslated region, CHIKV-viral RNA consistently showed a lower frequency of single-nucleotide polymorphisms than the 181/25 RNA including at the E2-12 and E2-82 residues previously identified as attenuating mutations. In the CHIKV-7, frequencies of reversions at E2-12 and E2-82 were 0.064% and 0.086%, while in the 181/25, frequencies were 0.179% and 0.133%, respectively. We conclude that the DNA-launched virus has a reduced probability of reversion mutations, thereby enhancing vaccine safety.

Original languageEnglish (US)
Pages (from-to)83-90
Number of pages8
JournalVirology
Volume490
DOIs
StatePublished - Mar 1 2016

Fingerprint

Chikungunya virus
DNA Sequence Analysis
Vaccines
Plasmids
Viruses
Mutation
DNA Vaccines
DNA Viruses
Viral RNA
3' Untranslated Regions
Pandemics
Single Nucleotide Polymorphism
Vaccination
Complementary DNA
Clone Cells
RNA
Safety
DNA

Keywords

  • Alphavirus
  • Chikungunya fever
  • Chikungunya virus
  • CHIKV
  • DNA vaccine
  • Live attenuated vaccine

ASJC Scopus subject areas

  • Virology

Cite this

Hidajat, R., Nickols, B., Forrester, N., Tretyakova, I., Weaver, S., & Pushko, P. (2016). Next generation sequencing of DNA-launched Chikungunya vaccine virus. Virology, 490, 83-90. https://doi.org/10.1016/j.virol.2016.01.009

Next generation sequencing of DNA-launched Chikungunya vaccine virus. / Hidajat, Rachmat; Nickols, Brian; Forrester, Naomi; Tretyakova, Irina; Weaver, Scott; Pushko, Peter.

In: Virology, Vol. 490, 01.03.2016, p. 83-90.

Research output: Contribution to journalArticle

Hidajat, R, Nickols, B, Forrester, N, Tretyakova, I, Weaver, S & Pushko, P 2016, 'Next generation sequencing of DNA-launched Chikungunya vaccine virus', Virology, vol. 490, pp. 83-90. https://doi.org/10.1016/j.virol.2016.01.009
Hidajat, Rachmat ; Nickols, Brian ; Forrester, Naomi ; Tretyakova, Irina ; Weaver, Scott ; Pushko, Peter. / Next generation sequencing of DNA-launched Chikungunya vaccine virus. In: Virology. 2016 ; Vol. 490. pp. 83-90.
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