Next generation sequencing of DNA-launched Chikungunya vaccine virus
Autor(es): Hidajat Rachmat, Nickols Brian, Forrester Naomi, Tretyakova Irina, Weaver Scott, Pushko Peter
Resumo: Chikungunya virus (CHIKV) represents a p-emic 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-7 encoding the full-length cDNA of the 181/25 vaccine. The DNA-launched CHIKV-7 virus was prepared - compared to the 181/25 virus. Illumina HiSeq2000 sequencing revealed that with the exception of the 3' untranslated region, CHIKV-7 viral RNA consistently showed a lower frequency of single-nucleotide polymorphisms than the 181/25 RNA including at the E2-12 - E2-82 residues previously identified as attenuating mutations. In the CHIKV-7, frequencies of reversions at E2-12 - E2-82 were 0.064% - 0.086%, while in the 181/25, frequencies were 0.179% - 0.133%, respectively. We conclude that the DNA-launched virus has a reduced probability of reversion mutations, thereby enhancing vaccine safety.
Palavras-Chave: Alphavirus; CHIKV; Chikungunya fever; Chikungunya virus; DNA vaccine; Live attenuated vaccine
Imprenta: Virology, v. 490, p. 83-90, 2016
Identificador do objeto digital: 10.1016/j.virol.2016.01.009
Descritores: Chikungunya virus - Cytopathology ; Chikungunya virus - DNA ; Chikungunya virus - RNA ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever
Data de publicação: 2016
