An innovative vaccine design to attenuate RNA viruses

Evolutionary virologists from the Viral Populations and Pathogenesis Unit at the Institut Pasteur in Paris worked in close collaboration with computational biologists and proposed an innovative way to challenge RNA viruses' great adaptive capacity. Precisely by using this adaptive potential (high mutation rates) that makes their strength but also their weakness: they can't correct errors in case of detrimental mutations.

Working on Coxsackie B3 and influenza A viruses, they engineered the viruses' genomes to drive their evolutionary trajectories towards detrimental regions in sequence space (the whole possible sequences for a gene). The modified viruses generated more Stop mutations, significantly reducing their viral fitness. In vivo experiments showed reduced virulence, the viruses generated high levels of neutralizing antibodies, and mice were protected against lethal challenge.

This is an innovative vaccine method, for which the Institut Pasteur has filed a patent application.

Marco Vignuzzi, head of the Viral Populations and Pathogenesis Unit at the Institut Pasteur, will be joining the faculty of our 14th HKU-Pasteur Virology course (6-14 July 2017). His lecture, "Genetic Diversity and Quasispecies" will be open to the public (11 July 2017, 9am).

On the left, a cell culture dish with wild-type enteroviruses. On the right, a dish containing genetically modified enteroviruses ("stop" mutations) with reduction in viral multiplication © Institut Pasteur

Attenuation of RNA viruses by redirecting their evolution in sequence space, Nature Microbiology, June 5, 2017. Gonzalo Moratorio1, Rasmus Henningsson1,2,3*, Cyril Barbezange1*, Lucia Carrau1,4, Antonio V. Bordería1,2, Hervé Blanc1, Stephanie Beaucourt1, EnzoZ.Poirier1,4, Thomas Vallet1, Jeremy Boussier2,5,6, BryanC.Mounce1, Magnus Fontes2,3 and Marco Vignuzzi1 1. Viral Populations and Pathogenesis Unit, Institut Pasteur, CNRS UMR 3569, 28 rue du Dr. Roux, 75724 Paris cedex 15, France. 2. International Group for Data Analysis, Institut Pasteur, C3BI, USR 3756 IP CNRS, 28 rue du Dr. Roux, 75724 Paris cedex 15, France. 3. Centre for Mathematical Sciences, Lund University, 22100 Lund, Sweden. 4. Sorbonne Paris Cité, Université Paris Diderot, Cellule Pasteur, 75013 Paris, France. 5. Unité d’Immunobiologie des Cellules Dendritiques, Institut Pasteur, Inserm 1223, 25 rue du Dr. Roux, 75724 Paris cedex 15, Paris, France. 6. Ecole doctorale Frontières du vivant, Université Paris Diderot, 75013 Paris, France.

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