Measles-virus based dengue vaccine
Up to 390 million infections of dengue are estimated to occur annually, of which 96 million have clinical manifestations. Dengue is estimated to cause 22,000 deaths every year, mainly among children. Although mortality is relatively lower compared to other tropical infectious diseases such as malaria, the scale of human suffering and the resources invested in the control of dengue make it a major global health problem. Several vaccine candidates for dengue are currently in pre-clinical or clinical development and the most advanced recently completed phase III efficacy trials and has been approved for licensure in endemic areas in Mexico, Philippines and Brazil. While this vaccine might be appropriate for certain regions of the world with limited dengue type exposure, all studies showed a disparity of serotype conversion and the risk of an antibody enhanced phenotype on exposure to another serotype, also described as the dengue viral interference problem. Furthermore, with observed vaccine enhanced disease symptoms in young children, the current partially licensed vaccine is only approved for adolescents and adults between nine to 45 years of age. Therefore a vaccine, which protects equally against all serotypes without interference problems, would reach a broader target group and be of added value for the population most at risk.
The primary objective is to demonstrate the proof-of concept of a measles-virus-dengue vaccine candidate (MVDVax) in a non-human primate model, with the ultimate long-term objective of developing an effective prevention tool for dengue. A second objective is the development of an assay to quantify the amount of envelope domain III expressed for each of the four dengue virus serotypes, and demonstrate consistent expression of proteins across vaccine batches.
MVDVax targets populations at risk of dengue infection including young children in dengue endemic regions and travellers to affected areas. Unlike other dengue vaccines candidates, MVDVax uses a single live dengue vaccine designed to activate both humoral and cellular immune response against the four serotypes of dengue virus simultaneously, thereby hopefully overcoming the viral interference problem. The current project will produce all data required for follow up projects in order to be able to commence good manufacturing practice (GMP) production, toxicology studies and phase I clinical trial.
- Demonstrate EDIII expression across MVDVax batches (completed)
- Finish immunisation
- Report on immunogenicity and efficacy of MVDVax
Brandler S, Ruffie C, Najburg V, Frenkiel MP, Bedouelle H, Desprès P, Tangy F. Pediatric measles vaccine expressing a dengue tetravalent antigen elicits neutralizing antibodies against all four dengue viruses. Vaccine. 2010 Sep 24