BACKGROUND

Advanced vaccine production techniques are expected by pharmaceutical industry.

2 types of vaccines are currently available:

• Attenuated viruses (modification of the viruses phenotype) but attenuation level is difficult to control
• Inactivated viruses are highly expensive as well as difficult to obtain and show limited efficiency on a short period (require multiple injections)

HOW IT WORKS

Combination of two novel methodologies:

• Obtention of attenuated virus (with a controlled attenuation level), by a randomized but controlled re-encoding approach
• Production of infectious virus by infectious-subgenomic-amplicons (ISA) produced by RT-PCR on the whole viral genome

Developed by Pr. Xavier DE LAMBALLERIE’s team, at “Viral Diseases Emergence” Lab (UMR_D 190, Medicine University of Marseille, FRANCE), scientific key opinion leader in vaccinology

KEY BENEFITS

• Control of undesired genomic mutations and of viral attenuation levels
• No possible escape by reversion (reversion level does not exceed 0,34% even after 200 cell cycles)
• No problem of clonal diversity, and high stability of the attenuated generated viruses
• Very low probability of recombination with a wild strain
• 1-month production (versus 5 months with standard method)
• Significant decrease of production costs (5-fold)

RESULTS

In vitro on Chikungunya (in primate and mosquito cells), and Tick-Borne Encephalitis attenuated viruses

In vivo: mice vaccinated in one shot with 1 000 000 cells of Tick-Borne Encephalitis attenuated or wild-type virus strains

• 43 days post-infection, 100% of the mice inoculated with the WT virus strains died
• No deaths occurred regarding the 20 mice inoculated with the re-encoded strains
• Surviving mice showed stable IgG levels and weight

APPLICATIONS

Human and veterinary single-stranded RNA viruses

Possible extension of the method to DNA viruses