Institut de Biologie StructuraleGrenoble / France

A chimeric pseudo-adenovirus to combat emergent diseases

Infectious diseases continue to decimate populations around the world. Among the means at our disposal to counter these threats, vaccination has proven to be exceptionally powerful. Smallpox has been eradicated, measles and polio are controlled by vaccination. However, serious threats still exist, as evidenced by epidemics caused by the Ebola or Zika viruses. Another recent example is the Chikungunya virus, a viral pathogen transmitted by the bite of a tiger mosquito. Once confined to sub-Saharan Africa, the Chikungunya virus has recently spread worldwide as these mosquito vectors move geographically up to the poles as a result of climate change.
The "Adenovirus" team of the Methods & Electron Microscopy group at IBS has formed an international consortium with EMBL and the University of Bristol to develop a new vaccine technology. Indeed, this team is working on an adenovirus protein that spontaneously self-assembles by 60 to give a particularly stable particle even without refrigeration, similar to a virus but not infectious. A cryo electron microscopy study showed that this particle has a very flexible quasi-spherical surface. Engineering of this adenoviral protein was then carried out to customarily replace these exposed regions with those from other pathogens. Proof of principle was established by expressing a particle displaying neutralizing epitopes of the Chikungunya virus. These chimeric neo-particles Adenovirus/Chikungunya have shown promising results in animal studies as shown both by their drainage to the lymph nodes and the humoral response produced against the epitopes of the Chikungunya virus covering the particle. This easy-to-use vaccine technology, based on a single particle that can be modified by synthetic biology, has been patented by the CNRS and EMBL and could eventually be used to fight many other infectious diseases. The results have just been published in the prestigious journal Science Advances.

Synthetic self-assembling ADDomer platform for highly efficient vaccination by genetically encoded multiepitope display. Charles Vragniau, Joshua C. Bufton, Frédéric Garzoni, Emilie Stermann, Fruzsina Rabi,Céline Terrat, Mélanie Guidetti, Véronique Josserand, Matt Williams, Christopher J. Woods, Gerardo Viedma, Phil Bates, Bernard Verrier, Laurence Chaperot, Christiane Schaffitzel, Imre Berger and Pascal Fender. Science Advances ; Vol. 5, no. 9, eaaw2853