ArticlePLoS neglected tropical diseases2015
Extended Preclinical Safety, Efficacy and Stability Testing of a Live-attenuated Chikungunya Vaccine Candidate.
Article in PLoS neglected tropical diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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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.
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Who cites it
40 citing papers in PubMed, 45 citations in OpenAlex.
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- Chikungunya virus: Current situation and future challenges.Biosafety and health · 2025Review
- Pathogenesis and clinical management of arboviral diseases.World journal of virology · 2025Review
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- Single-Dose Immunogenic DNA Vaccines Coding for Live-Attenuated Alpha- and Flaviviruses.Viruses · 2024Review
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- Evolution and immunopathology of chikungunya virus informs therapeutic development.Disease models & mechanisms · 2023Review
- Replication Kinetics of a Candidate Live-Attenuated Vaccine for Cache Valley Virus inVector borne and zoonotic diseases (Larchmont, N.Y.) · 2022Article
- A Review on Chikungunya Virus Epidemiology, Pathogenesis and Current Vaccine Development.Viruses · 2022Review
- Chikungunya Virus Vaccines: Platforms, Progress, and Challenges.Current topics in microbiology and immunology · 2022Review
- The global burden of Chikungunya fever among children: A systematic literature review and meta-analysis.PLOS global public health · 2022Article
- The research progress of Chikungunya fever.Frontiers in public health · 2022Review
- Live-attenuated RNA hybrid vaccine technology provides single-dose protection against Chikungunya virus.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Prophylactic strategies to control chikungunya virus infection.Virus genes · 2021Review
- Novel insights into the treatment of SARS-CoV-2 infection: An overview of current clinical trials.International journal of biological macromolecules · 2020Review
- Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose.Vaccines · 2020Article
- Chikungunya virus replication in skeletal muscle cells is required for disease development.The Journal of clinical investigation · 2020Article
- Chikungunya infection: de-linking replication from symptomatology reveals the central role of muscle.The Journal of clinical investigation · 2020Article
- "Submergence" of Western equine encephalitis virus: Evidence of positive selection argues against genetic drift and fitness reductions.PLoS pathogens · 2020Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
We recently described a new, live-attenuated vaccine candidate for chikungunya (CHIK) fever, CHIKV/IRES. This vaccine was shown to be well attenuated, immunogenic and efficacious in protecting against CHIK virus (CHIKV) challenge of mice and nonhuman primates. To further evaluate its preclinical safety, we compared CHIKV/IRES distribution and viral loads in interferon-α/β receptor-incompetent A129 mice to another CHIK vaccine candidate, 181/clone25, which proved highly immunogenic but mildly reactive in human Phase I/II clinical trials. Compared to wild-type CHIK virus, (wt-CHIKV), both vaccines generated lower viral loads in a wide variety of tissues and organs, including the brain and leg muscle, but CHIKV/IRES exhibited marked restrictions in dissemination and viral loads compared to 181/clone25, and was never found outside the blood, spleen and muscle. Unlike wt-CHIKV, which caused disrupted splenic architecture and hepatic lesions, histopathological lesions were not observed in animals infected with either vaccine strain. To examine the stability of attenuation, both vaccines were passaged 5 times intracranially in infant A129 mice, then assessed for changes in virulence by comparing parental and passaged viruses for footpad swelling, weight stability and survival after subcutaneous infection. Whereas strain 181/clone25 p5 underwent a significant increase in virulence as measured by weight loss (from <10% to >30%) and mortality (from 0 to 100%), CHIKV/IRES underwent no detectible change in any measure of virulence (no significant weight loss and no mortality). These data indicate greater nonclinical safety of the CHIKV/IRES vaccine candidate compared to 181/clone25, further supporting its eligibility for human testing.
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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.