ArticleJournal of virology2012
Attenuation of Chikungunya virus vaccine strain 181/clone 25 is determined by two amino acid substitutions in the E2 envelope glycoprotein.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.
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.
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.
Who cites it
138 citing papers in PubMed, 197 citations in OpenAlex.
- Live-attenuated chikungunya vaccine in children: a randomized phase 2 trial.Nature medicine · 2026Trial
- Safety and immunogenicity of a single-shot live-attenuated chikungunya vaccine: a double-blind, multicentre, randomised, placebo-controlled, phase 3 trial.Lancet (London, England) · 2023Trial
- Optimized Amplicon Strategy for Long-Read Sequencing of the Chikungunya Virus Genome.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Chikungunya virus nsP2: Insights into viral replication, pathogenesis, and therapeutic targeting.Virulence · 2026Review
- Global resurgence of Chikungunya virus: outbreak drivers and emerging solutions.Emerging microbes & infections · 2026Review
- Live imaging and interactome analysis of Zika and chikungunya viral RNAs via dual-action aptamer tag.Nature communications · 2026Article
- Chikungunya Virus E2 N218K Enhances Heparan Sulfate-Dependent Attachment and Viral Internalization While Conferring Partial Attenuation in A129 Mice.Pathogens (Basel, Switzerland) · 2026Article
- Cell type-dependent induction of type I interferon and PARP1 activation in astrocytes and neurons during chikungunya virus infection.Microbiology spectrum · 2026Article
- Luciferase unleashed: Lighting the path to vaccine approval using a novel high-throughput chikungunya virus neutralization assay.PLoS neglected tropical diseases · 2026Article
- Article
- Integrated reiterative pipeline for rapid epitope-based pan-alphavirus vaccines.Science advances · 2026Article
- Article
- E2 Protein of Chikungunya Virus: A Narrative Review of Its Potential as a Therapeutic Target.Current drug targets · 2026Review
- Attenuated viral strains of priority pathogens for potential use in controlled human infection model studies: A scoping review.PLoS neglected tropical diseases · 2026Article
- Article
- Chikungunya virus: Current situation and future challenges.Biosafety and health · 2025Review
- Old World alphaviruses use distinct mechanisms to infect brain microvascular endothelial cells for neuroinvasion.Cell reports · 2025Article
- The Construction and Characterization of an Infectious Clone of the Asian Genotype Chikungunya Virus from Yunnan, China.Tropical medicine and infectious disease · 2025Article
- γδ T Cells Mediate Protective Immunity Following Vaccination with an Insect-Based Chikungunya Fever Vaccine in Mice.Pathogens (Basel, Switzerland) · 2025Article
- Determinants of human versus mosquito cell entry by the Chikungunya virus envelope proteins.bioRxiv : the preprint server for biology · 2025Article
78 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Chikungunya virus (CHIKV) is the mosquito-borne alphavirus that is the etiologic agent of massive outbreaks of arthralgic febrile illness that recently affected millions of people in Africa and Asia. The only CHIKV vaccine that has been tested in humans, strain 181/clone 25, is a live-attenuated derivative of Southeast Asian human isolate strain AF15561. The vaccine was immunogenic in phase I and II clinical trials; however, it induced transient arthralgia in 8% of the vaccinees. There are five amino acid differences between the vaccine and its parent, as well as five synonymous mutations, none of which involves cis-acting genome regions known to be responsible for replication or packaging. To identify the determinants of attenuation, we therefore tested the five nonsynonymous mutations by cloning them individually or in different combinations into infectious clones derived from two wild-type (WT) CHIKV strains, La Reunion and AF15561. Levels of virulence were compared with those of the WT strains and the vaccine strain in two different murine models: infant CD1 and adult A129 mice. An attenuated phenotype indistinguishable from that of the 181/clone 25 vaccine strain was obtained by the simultaneous expression of two E2 glycoprotein substitutions, with intermediate levels of attenuation obtained with the single E2 mutations. The other three amino acid mutations, in nsP1, 6K, and E1, did not have a detectable effect on CHIKV virulence. These results indicate that the attenuation of strain 181/clone 25 is mediated by two point mutations, explaining the phenotypic instability observed in human vaccinees and also in our studies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.