Could a temperature-resistant vaccine spell the end for rabies and yellow fever?

Rabies and yellow fever claim tens of thousands of lives every year. Although vaccines do exist, they are either expensive or in short supply. In addition, they need to be transported and stored at controlled temperatures. A consortium led by KU Leuven aims to tackle all of these issues by developing a cheap, temperature-stable, and easy-to-produce vaccine against both diseases simultaneously.


Rabies and yellow fever claim tens of thousands of lives every year. Although vaccines do exist, they are either expensive or in short supply. In addition, they need to be transported and stored at controlled temperatures. A consortium led by KU Leuven aims to tackle all of these issues by developing a cheap, temperature-stable, and easy-to-produce vaccine against both diseases simultaneously.

With a near 100% fatality rate, rabies is one of the deadliest diseases on Earth. It claims an estimated 58,000 lives per year, most of these in remote areas of Africa and Asia and more than half of them children. Many people are not vaccinated because the vaccines are expensive and they need to be transported via the cold chain. If given prophylactically, three doses are needed, while up to five are required to be effective after exposure.

Mosquito-borne yellow fever can cause a life-threatening infection with jaundice, systemic bleeding, shock, and organ failure. Although safe and highly efficient prophylactic vaccines are available, an estimated 30,000 people die from the disease each year because of inadequate supplies, the need for trained staff, and a cold chain transportation requirements.

Funded by a €4.1m grant from the EU's Horizon 2020 Research and Innovation Programme, the RABYD-VAX Consortium combines the expertise of researchers from four European institutions. Led by Johan Neyts at the KU Leuven Laboratory of Virology, it hopes to address these issues by developing a vaccine that protects against both rabies and yellow fever that could be included in routine childhood vaccinations. The vaccine will be developed to be cheap, temperature-stable, easy-to-produce on a large scale, and administered without a needle.

The platform

The new rabies / yellow fever vaccine will be created using novel platform technology plasmid-launched live-attenuated vaccine (PLLAV), which was developed by KU Leuven’s Dr Kai Dallmeier. His team has cloned the commercial yellow fever genome into a bacterial artificial chromosome, or DNA plasmid, which can then have other antigens inserted.

"The team has cloned the commercial yellow fever genome into a bacterial artificial chromosome."

RABYD-VAX’s project manager Lotte Coelmont said: “Our technology combines the advantages of live-attenuated vaccines and DNA vaccines without dragging along their drawbacks.” 

One of the most important advantages of the PLLAV technology, compared to other commercially available vaccines, is that it does not need a cold chain due to the physical and genetic stability of DNA-based vaccines. In addtion, the vaccine can be produced in large volumes in fermenters, avoiding the need for cell cultures or embryonated chicken eggs.

The project

Coelmont says: “The first step was to clone the rabies antigen inside the yellow fever genome of our technology. If we hadn’t come up with a good construct that replicated well, the rest of the project would have been jeopardised.

“We are now on the second generation of constructs, which replicated even better than the first, so we hope that by summer, our research partners can start testing these for immunogenicity.”

The team will conduct a set of tests designed to gain deeper insight into the vaccine’s immune response against the rabies virus, as well as to explore the potential for the rabies / yellow fever vaccine to protect against other viruses in the same family as rabies.

Coelmont adds: “Rabies belongs to the lyssavirus group and we’d ultimately like to be able to protect against other rabies strains that may pop up in the future.”

During the four years of the RABYD-VAX project, the researchers also hope to gain novel insights into the PLLAV technology and its potential to target indications besides rabies. There may also be the possibility to use a different virus  in the same family as yellow fever.

"Zika virus and Japanese encephalitis belong to the same genus of viruses as yellow fever."

Coelmont explans: “Zika virus and Japanese encephalitis belong to the same genus of viruses as yellow fever, they are all flaviviruses. 

“In theory, we could change the backbone of the PLLAV technology to one of these and combine different indications depending on the region of vaccine application.

“We could combine Japanese encephalitis with rabies for Asia and yellow fever with rabies for the other regions." 

Also a mosquito-borne virus, there are an estimated 68,000 clinical cases of Japanese encephalitis every year. The fatality rate is up to 30% and more than 3 billion people are at risk of infection.

The ultimate goal

By the end of the RABYD-VAX project, the team hopes to reach the advanced pre-clinical stage of the rabies / yellow fever vaccine's development, but it will be at least 10 years before it will be available to patients.

Coelmont explains: “As part of our four-year project, we have a contractor that will do a market study to find out what we will need to have in place to go to the clinical phase.

“Then we can move forward towards clinical trials, but a lot depends on how the regulatory approval process goes.

“Today, patients need to return to healthcare facilities up to five times for rabies vaccines, which is just not possible for many people.

“We are aiming for a one-dose rabies / yellow fever childhood vaccine, which would be integrated into the standard vaccination programme of endemic regions and administered at around nine months. Patients would then ideally have lifelong protection against rabies.”