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1toStopVax SIGNED

RNA virus attenuation by altering mutational robustness

Total Cost €

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EC-Contrib. €

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Partnership

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 1toStopVax project word cloud

Explore the words cloud of the 1toStopVax project. It provides you a very rough idea of what is the project "1toStopVax" about.

extreme    attenuating    stop    detrimental    rate    conventional    becomes    attenuation    ing    universally    strategies    victim    trait    genetic    physical    faces    viruses    buffer    generates    reversion    viral    complete    broad    replicates    levels    mutations    proof    proportion    survival    changing    ve    variants    types    antibody    biological    applicability    rna    genome    places    larger    protected    families    away    negative    fitness    errors    species    lethal    infection    mutation    mice    cloud    nucleotide    neutralizing    naturally    majority    phenotype    virus    rational    industrial    population    potentially    beneficial    variety    robustness    confirming    hence    mutational    preclinical    commercialization    attenuated    pathogenic    mostly    modifiable    attenuates    creates    vaccine    empirical    modified    diversity    instability    vivo    succeeded    frequencies   

Project "1toStopVax" data sheet

The following table provides information about the project.

Coordinator
INSTITUT PASTEUR 

Organization address
address: RUE DU DOCTEUR ROUX 25-28
city: PARIS CEDEX 15
postcode: 75724
website: http://www.pasteur.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country France [FR]
 Total cost 150˙000 €
 EC max contribution 150˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-PoC
 Funding Scheme ERC-POC
 Starting year 2016
 Duration (year-month-day) from 2016-09-01   to  2018-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT PASTEUR FR (PARIS CEDEX 15) coordinator 150˙000.00

Map

 Project objective

RNA viruses have extreme mutation frequencies. When a RNA virus replicates, nucleotide mutations are generated resulting in a population of variants. This genetic diversity creates a cloud of mutations that are potentially beneficial to viral survival, but the majority of mutations are detrimental to the virus. By increasing the mutation rate of a RNA virus, viral fitness is reduced because it generates more errors, and attenuates the virus during in vivo infection. Another feature that affects RNA virus fitness is mutational robustness. Mutational robustness is the ability to buffer the negative effects of mutation. The attenuation of RNA viruses for vaccine production faces problems of genetic instability and reversion to a pathogenic phenotype. The conventional method for attenuation is mostly empirical and specific to the particular RNA virus species.
Hence, it cannot be universally applied to a variety of virus types. We've developed a non-empirical, rational means of attenuating RNA viruses, targeting mutational robustness as modifiable trait.
 We demonstrate that mutational robustness of RNA viruses can be modified without changing a virus' physical and biological properties for vaccine production; yet the virus is attenuated as it becomes victim of its naturally high mutation rate. Specifically, the genome of RNA viruses are modified so that a larger proportion of mutations become lethal Stop mutations. Our technology places the virus one step away from these Stop mutations (1-to-Stop). We succeeded in attenuating two RNA viruses from very different viral families, confirming the broad applicability of this approach. These viruses were attenuated in vivo, generated high levels of neutralizing antibody and protected mice from lethal challenge infection. The proposal now seeks to complete proof of concept studies and develop commercialization strategies to scale up this new technology to preclinical testing with industrial partners.

 Publications

year authors and title journal last update
List of publications.
2017 Gonzalo Moratorio, Rasmus Henningsson, Cyril Barbezange, Lucia Carrau, Antonio V. Bordería, Hervé Blanc, Stephanie Beaucourt, Enzo Z. Poirier, Thomas Vallet, Jeremy Boussier, Bryan C. Mounce, Magnus Fontes, Marco Vignuzzi
Attenuation of RNA viruses by redirecting their evolution in sequence space
published pages: 17088, ISSN: 2058-5276, DOI: 10.1038/nmicrobiol.2017.88
Nature Microbiology 2 2019-06-12

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