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

7 Scopus citations

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

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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