Genetic and neuroattenuation phenotypic characteristics and their stabilities of SA14-14-2 vaccine seed virus

Liu, Xinyu; Zhao, Danhua; Jia, Lili; Xu, Huailiang; Na, Rui; Ge, Yonghong; ShaoXiang, Liu; Yu, Yongxin; Li, Yuhua

doi:10.1016/j.vaccine.2018.06.040

Cited by 11 publications

(18 citation statements)

References 19 publications

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“…The WT strain SA14 used in our studies was found to have three to eleven nucleotide changes encoding two to six amino acid substitutions compared to previously published SA14 strain sequences 10 , 12 . None of these changes were conserved across GenBank submissions though one change, 1708 (E-G244E), was reported in five of six publications.…”

Section: Resultsmentioning

confidence: 64%

“…The SA14-14-2 stock used in our studies differed from all previously published isolates by four nucleotides that encoded one synonymous change at nucleotide 9122 and three non-synonymous consensus changes at nucleotides 1117 (E-N47S), 1512 (E-K179E) and 7656 (NS4B-D131N) 10 , 51 , 52 (Table 1 ). As residues E-47N, E-179K and NS4B-131D were present in all previously published SA14-14-2 strains and in progenitor Clone12-1-7 (Genbank submission: AF416457), it can be presumed that these residues constitute part of a conserved vaccine genotype.…”

Section: Resultsmentioning

confidence: 93%

“…SNVs were detected at the position of three synonymous mutations differentiating the published sequences and the SA14 used here (NS2B-71, NS3-275 and NS4A-58); however, the nucleotide detected as a SNV was not the same as the nucleotide in the published sequence. No SNVs were detected at E-107 or E-138, which have been shown to be virulence determinants of SA14 10 , 11 . This reinforces our hypothesis that the WT SA14 is naturally genotypically heterogeneous, leading to consensus sequences that vary from sample to sample due to the expansion of subpopulations of viral RNA species.…”

Section: Resultsmentioning

confidence: 95%

“…WT JEV infection has been modeled using adult and suckling mice, and multiple outbred and inbred strains 10 , 11 , 13 , 17 , 31 , 34 , 45 – 49 . In general, other than newborn mice, WT JEV strains only cause a lethal infection when given intracranially or by a peripheral route after the blood brain barrier has been perturbed whereas it has been shown that SA14-14-2 is avirulent in suckling mice by both intracranial and intraperitoneal routes (Yang, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Japanese encephalitis virus live attenuated vaccine strains display altered immunogenicity, virulence and genetic diversity

Davis

Beck

et al. 2021

npj Vaccines

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Japanese encephalitis virus (JEV) is the etiological agent of Japanese encephalitis (JE). The most commonly used vaccine used to prevent JE is the live-attenuated strain SA14-14-2, which was generated by serial passage of the wild-type (WT) JEV strain SA14. Two other vaccine candidates, SA14-5-3 and SA14-2-8 were derived from SA14. Both were shown to be attenuated but lacked sufficient immunogenicity to be considered effective vaccines. To better contrast the SA14-14-2 vaccine with its less-immunogenic counterparts, genetic diversity, ribavirin sensitivity, mouse virulence and mouse immunogenicity of the three vaccines were investigated. Next generation sequencing demonstrated that SA14-14-2 was significantly more diverse than both SA14-5-3 and SA14-2-8, and was slightly less diverse than WT SA14. Notably, WT SA14 had unpredictable levels of diversity across its genome whereas SA14-14-2 is highly diverse, but genetic diversity is not random, rather the virus only tolerates variability at certain residues. Using Ribavirin sensitivity in vitro, it was found that SA14-14-2 has a lower fidelity replication complex compared to SA14-5-3 and SA14-2-8. Mouse virulence studies showed that SA14-2-8 was the most virulent of the three vaccine strains while SA14-14-2 had the most favorable combination of safety (virulence) and immunogenicity for all vaccines tested. SA14-14-2 contains genetic diversity and sensitivity to the antiviral Ribavirin similar to WT parent SA14, and this genetic diversity likely explains the (1) differences in genomic sequences reported for SA14-14-2 and (2) the encoding of major attenuation determinants by the viral E protein.

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Section: Resultsmentioning

confidence: 64%

Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Japanese encephalitis virus live attenuated vaccine strains display altered immunogenicity, virulence and genetic diversity

Davis

Beck

et al. 2021

npj Vaccines

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show abstract

“…Moreover, the results of the studies of the full-length gene sequences of SA14-14-2 demonstrated its high genetic and phenotypic stabilities. The neurovirulence of this vaccine is relatively low and will remain largely unchanged [ 108 ]. The establishment of genetic and attenuated neurovirulence characteristics and the stabilities of SA14-14-2 virus are important in relation to vaccine safety in humans.…”

Section: Vaccines Of Flavivirusmentioning

confidence: 99%

Flavivirus: From Structure to Therapeutics Development

Zhao

Wang

Cao

et al. 2021

Life

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Flaviviruses are still a hidden threat to global human safety, as we are reminded by recent reports of dengue virus infections in Singapore and African-lineage-like Zika virus infections in Brazil. Therapeutic drugs or vaccines for flavivirus infections are in urgent need but are not well developed. The Flaviviridae family comprises a large group of enveloped viruses with a single-strand RNA genome of positive polarity. The genome of flavivirus encodes ten proteins, and each of them plays a different and important role in viral infection. In this review, we briefly summarized the major information of flavivirus and further introduced some strategies for the design and development of vaccines and anti-flavivirus compound drugs based on the structure of the viral proteins. There is no doubt that in the past few years, studies of antiviral drugs have achieved solid progress based on better understanding of the flavivirus biology. However, currently, there are no fully effective antiviral drugs or vaccines for most flaviviruses. We hope that this review may provide useful information for future development of anti-flavivirus drugs and vaccines.

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