Evidence map›Paper›PMID 34475404›Full record

ArticleNPJ vaccines2021

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

Emily H Davis, Andrew S Beck, Li Li, Mellodee M White, Marianne Banks Greenberg, Jill K Thompson, Steven G Widen, Alan D T Barrett, Nigel Bourne

Open access · goldAbstract read
In one paragraph

Article in NPJ vaccines, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.3field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 28 citations in OpenAlex.

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  8. West Nile virus unmasked: from gene variability to future challenges.Frontiers in cellular and infection microbiology · 2025
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  17. Review
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Emily H Davis *Department of Pathology, The University of Texas Medical Branch, Galveston, TX, USA.
Andrew S Beck *Department of Pathology, The University of Texas Medical Branch, Galveston, TX, USA.ORCID http://orcid.org/0000-0001-5307-5565
Li LiDepartment of Pathology, The University of Texas Medical Branch, Galveston, TX, USA.
Mellodee M WhiteDepartment of Pediatrics, The University of Texas Medical Branch, Galveston, TX, USA.ORCID http://orcid.org/0000-0003-1728-0451
Marianne Banks GreenbergDepartment of Pediatrics, The University of Texas Medical Branch, Galveston, TX, USA.
Jill K ThompsonDepartment of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA.
Steven G WidenDepartment of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA.
Alan D T BarrettDepartment of Pathology, The University of Texas Medical Branch, Galveston, TX, USA. abarrett@utmb.edu.ORCID http://orcid.org/0000-0003-3740-7448
Nigel BourneDepartment of Pediatrics, The University of Texas Medical Branch, Galveston, TX, USA. nibourne@utmb.edu.
The University of Texas Medical Branch at Galveston · USCenters for Disease Control and Prevention · US

Funding

Biodefense Training ProgramT32AI060549 · NIAID · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI ASHOK K CHOPRA, Janice J Endsley · 2004 to 2026
$3.0M
Preclinical development of candidate Zika virus vaccines using mouse modelsR21AI129844 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI BARRETT, ALAN D.T. · 2017 to 2018
$433k
Gillson Longenbaugh Foundation NoneNIAID NIH HHS R21 AI129844NIAID NIH HHS T32 AI060549U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R21 AI 129844U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) T32 AI 060549
6 · The paper itself

Abstract

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.

Identifiers

PMID34475404
PMCPMC8413339
OpenAlexW3198281243

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.