IrsiCaixa coordinates €5 Million EU-funded research project to tackle globally prevalent West Nile Virus

The IrsiCaixa AIDS Research Institute IrsiCaixa –a centre jointly promoted by the "la Caixa" Foundation and the Department of Health of the Generalitat de Catalunya– will receive 5.7 million euros from the European research programme Horizon-Europe to design therapies to tackle the effects of the West Nile Virus (WNV), an emerging pathogen which lacks treatments and for which there is no human vaccine.

IrsiCaixa, in collaboration with the University of Montpellier, Technische Universität Braunschweig, the University of Copenhagen, the Centre for Genomic Regulation (CRG), HIPRA, and the Barcelona Supercomputing Center - Centro Nacional de Supercomputación (BSC-CNS), will work on developing a safe and effective prophylactic vaccine against WNV which can induce a prolonged immune response and protect the entire population.

The project is called Limiting West Nile Virus Impact by Novel Vaccines And Therapeutics Approaches (LWNVIVAT). In addition to the vaccine, the scientific team will also design, produce, and analyse the efficacy and therapeutic potential of specific antibodies for the virus.

"We know this is an emerging pathogen, meaning its incidence is increasing globally. Having strategies to combat this virus could help thousands of people infected annually, but it would also be a very useful tool for future threats", explains Jorge Carrillo, project coordinator and principal investigator at IrsiCaixa.

WNV, one of the most widespread pathogens in the world

The West Nile Virus is globally widespread and uses mosquitoes as its transmission vector. While it is often asymptomatic, 1% of cases develop a severe disease which affects the central nervous system and which can ultimately lead to death. "For immunocompromised individuals and those over 60 years old, the mortality rate rises to 30%, highlighting the urgent need to find a solution which can protect vulnerable groups", says Carrillo.

In Spain, the first case of the disease was detected in 2010. Since then, various outbreaks have been identified across the country, including one in Andalusia in 2020, which led to 77 meningitis cases and caused 8 deaths. "Climate change favours the spread of mosquito-borne viruses like WNV. This is why it's crucial to understand health from a One Health perspective, integrating the study of animal and environmental health in addressing human health", Carrillo points out.

In search of a prophylactic vaccine

The main objective is to work on designing a vaccine capable of preventing infection by all genetic variants of WNV and offering protection to the entire population. "With computational tools, we can predict which molecules can activate the immune system and generate specific antibodies against the virus to combat it", says Victor Guallar, researcher at BSC-CNS. Once the molecules with most potential are identified, the next step is to produce them. To do this, collaborating institutions of the project will use different strategies: recombinant proteins and Virus-Like Particles (VLPs).

"One of the advantages of recombinant proteins, which are artificially produced in the laboratory, is that they can be easily generated in large quantities and at relatively low cost. This is useful for helping translate the vaccine for clinical use," explains Carlo Carolis, Head of the Protein Technologies Unit. VLPs, as their name suggests, are particles almost identical in structure and organization to viruses but non-infectious. The research team plans to use these constructs as a transport vehicle for the molecules of interest, so they induce an immune response in the human body. "Thanks to our ongoing platform of VLP-based vaccines to combat HIV, we can use all the knowledge and experience we’ve gained to adapt it to the West Nile Virus", says Julià Blanco, IGTP researcher at IrsiCaixa. "It's a good prophylactic strategy as VLPs are very stable structures capable of inducing a very potent immune response", he adds.

Refining vaccine efficacy with antibodies

The scientific team of LWNVIVAT, comprising researchers from eight research centres across four different countries, will test the efficacy of both the vaccine and antibodies.

"Parallel to the vaccine, we will also work on designing antibodies that can be used as treatment for WNV. Analysing the antibodies produced in response to the vaccine will greatly help identify new points of interest on the virus and refine the vaccine-induced response", explains Carrillo.

The production of these highly specific antibodies would allow their administration for both therapeutic and preventive purposes as a strategy to avoid new infections in the most vulnerable groups present in the geographic areas where there are WNV outbreaks.

WNV belongs to the flavivirus family, which also includes the dengue, Zika, and yellow fever viruses, among others. "Accumulating knowledge about WNV would not only allow us to develop treatment strategies against this virus but also provide the necessary tools to confront other viruses in the same family", concludes Carrillo.