ArticleNature medicine2012
A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers, 2 of them syntheses that pooled 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.
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
166 citing papers in PubMed, 2 syntheses or guidelines pooled it, 239 citations in OpenAlex.
- The Reassessed Potential of SARS-CoV-2 Attenuation for COVID-19 Vaccine Development-A Systematic Review.Viruses · 2022Pooled it
- COVID-19 Coronavirus Vaccine Design Using Reverse Vaccinology and Machine Learning.Frontiers in immunology · 2020Pooled it
- Effect of inhaled interferon-β1a on SARS-CoV-2 diversity and evolution.Microbiology spectrum · 2026Trial
- Recovery of proofreading-impaired SARS-CoV-2 reveals a mutator phenotype and an ExoN activity threshold for viability.Journal of virology · 2026Article
- Reverse genetics strategies for coronaviruses: platform construction and applications in vaccine development.Virus genes · 2026Review
- Article
- Recovery of proofreading-impaired SARS-CoV-2 reveals a mutator phenotype and an ExoN activity threshold for viability.bioRxiv : the preprint server for biology · 2026Article
- Mutation in enterovirus 71 nonstructural protein 3A increases genome replication fidelity and exhibits attenuated virulence in mice.Journal of virology · 2025Article
- Rapid development of attenuated IBV vaccine candidates through a versatile backbone applicable to variants.NPJ vaccines · 2025Article
- The coronavirus nsp14 exoribonuclease interface with the cofactor nsp10 is essential for efficient virus replication and enzymatic activity.Journal of virology · 2025Article
- Animal models of Long Covid: A hit-and-run disease.Science translational medicine · 2024Review
- A recombination-resistant genome for live attenuated and stable PEDV vaccines by engineering the transcriptional regulatory sequences.Journal of virology · 2023Article
- Virus hijacking of host epigenetic machinery to impair immune response.Journal of virology · 2023Review
- Neurological sequelae of vaccines.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Review
- Article
- Article
- Positive-strand RNA viruses-a Keystone Symposia report.Annals of the New York Academy of Sciences · 2023Article
- A review on structural, non-structural, and accessory proteins of SARS-CoV-2: Highlighting drug target sites.Immunobiology · 2023Review
- Vaccine development for zoonotic viral diseases caused by positive‑sense single‑stranded RNA viruses belonging to theExperimental and therapeutic medicine · 2023Review
- Scaling Biosafety Up During and Down After the COVID-19 Pandemic.Applied biosafety : journal of the American Biological Safety Association · 2022Review
106 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
6 authors at 2 institutions in 1 country.
Funding
Abstract
Live, attenuated RNA virus vaccines are efficacious but subject to reversion to virulence. Among RNA viruses, replication fidelity is recognized as a key determinant of virulence and escape from antiviral therapy; increased fidelity is attenuating for some viruses. Coronavirus (CoV) replication fidelity is approximately 20-fold greater than that of other RNA viruses and is mediated by a 3'→5' exonuclease (ExoN) activity that probably functions in RNA proofreading. In this study we demonstrate that engineered inactivation of severe acute respiratory syndrome (SARS)-CoV ExoN activity results in a stable mutator phenotype with profoundly decreased fidelity in vivo and attenuation of pathogenesis in young, aged and immunocompromised mice. The ExoN inactivation genotype and mutator phenotype are stable and do not revert to virulence, even after serial passage or long-term persistent infection in vivo. ExoN inactivation has potential for broad applications in the stable attenuation of CoVs and, perhaps, other RNA viruses.
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.