Periodic Reporting for period 4 - RABYD-VAX (Development of a Next-Generation, Dual-Target Rabies/Flavivirus Infectious DNA (iDNA) Vaccine)
Période du rapport: 2021-07-01 au 2021-12-31
The yellow fever virus (YFV), a mosquito-borne flavivirus, causes severe and life-threatening infections with jaundice, systemic bleeding, shock and multi-organ failure. An estimated 900 million people living in 45 endemic countries of Africa and Latin America are at high risk of infection. Although safe and highly efficient live-attenuated prophylactic vaccines [YFV-17D, Stamaril® and YF-Vax®] are available, an estimated 200,000 cases of yellow fever still occur annually, resulting in ~30,000 deaths (www.who.int) because of inadequate supplies, the need for trained staff for administration and a cold chain.
The Japanese encephalitis virus (JEV), also a mosquito-borne flavivirus, causes viral encephalitis in many countries of Asia, with an estimated 68,000 clinical cases every year. The case-fatality rate among the patients that develop encephalitis is up to 30%, permanent neurologic or psychiatric sequelae is reported in 30-50%. As for rabies, it is primarily a children’s disease. More than 3 billion people are at risk of infection.
During the course of the RABYD-VAX project, five European research institutes combined their expertise to develop and validate a new vaccine that protects against both rabies and yellow fever/Japanese encephalitis virus. This vaccine is based on a novel proprietary vaccine technology (i.e. PLLAV, plasmid-launched live-attenuated viral vaccine platform), which has been developed by the team of the project coordinator (KU Leuven) and which has several advantages over the currently used commercial vaccines. Ultimately, this vaccine could be given as a prophylactic childhood vaccine after incorporation in the standard childhood vaccination schedule of endemic regions and this, side-by-side, with domestic and wildlife animal vaccination programs to eradicate rabies.
In fact, the PLLAV technology addresses the need for good vaccines for the developing world as articulated by MSF “developing vaccines that are better adapted to reach children in remote or unstable locations – vaccines that do not require refrigeration, and that can be given in fewer doses […], paying enough attention to getting vaccine prices down”.
Current rabies vaccines need multiple dosing in order to induce virus neutralising antibodies that confer protection in individuals following exposure to RABV. In developing countries, where both YF and rabies cases are endemic, vaccination is often unaffordable. The results from this study have supported the feasibility of making a dual YF/RABV vaccine and the effect of the vaccine in protecting animals from lethal rabies challenge after one dose of vaccination. The new vaccine has the potential to make vaccination more accessible and easier to administer in resource-limited countries.