July 2024. An official report confirms the circulation of the Crimean-Congo virus in Galicia. The Galician Vector Surveillance Network, under the Department of Health, verified the detection of the pathogen in 13 farm animals and issued a reassuring message: human transmission is remote but increasingly probable. Despite this, the identification of the tick-borne virus raised alarms due to its up to 40% fatality rate and the six lives it has already claimed in Spain. Currently, there is no vaccine or specific treatment for this disease, but a CiQUS team has been working for years to find a solution.
The Molecular Virology group, led by José Martínez Costas at the Center for Research in Biological Chemistry and Molecular Materials (CiQUS), has been developing a vaccine candidate against Crimean-Congo in collaboration with a team at the Animal Health Research Center (CISA) in Madrid, where experiments were conducted. They are on the verge of publishing a study presenting preliminary results of their proposal.
The experiment at CISA involved injecting the virus into mice and then applying formulations proposed by CiQUS and the National Institute for Agricultural and Food Research and Technology (INIA-CSIC). The immune response against the viral protein, which forms the basis of the vaccine candidate, was then analyzed. "By combining the two technologies, we saw a much stronger response than with either system alone," said Martínez Costas. He emphasized, "The response in mice is overwhelming."
However, the CiQUS researcher stressed that they are still far from achieving a vaccine against Crimean-Congo, as their proposal is still in its early stages. The next step would be to test the formulation in a biosafety level 4 laboratory, the highest level where experiments with dangerous microorganisms are conducted. Since Spain lacks such a facility—CISA is classified as level 3—they would need to seek international collaboration.
Despite the challenges ahead, the team has made significant progress. For this vaccine candidate, the CiQUS team employed a proprietary protein encapsulation methodology using a Crimean-Congo nucleoprotein. "This approach is not typical in vaccine design, which usually involves surface proteins to generate antibodies that block viral entry into cells," explained Martínez Costas. However, the Galician proposal uses an internal viral protein.
"Crimean-Congo has considerable sequence variability in its external proteins, but the nucleoprotein we are working with is highly conserved," Martínez Costas noted. People who recovered from the hemorrhagic fever developed a strong cellular response against this nucleoprotein, suggesting it could be key to a future vaccine.
This method is not new for the team, as they successfully applied a similar approach to develop a vaccine against bluetongue disease, which affects both domestic and wild ruminants. "We created a fully sterilizing vaccine using a non-structural protein that the virus produces in infected cells," recalled Martínez Costas. The vaccine provided cross-protection due to the conserved nature of the protein, similar to what they aim for with Crimean-Congo.
The next steps involve testing the vaccine candidate's efficacy in susceptible animals and eventually in a level 4 biosafety laboratory. The team has applied to the European ISIDORe program for access to such facilities.
"Crimean-Congo is still an emerging disease in Spain but is increasingly detected in ticks and various regions, including Galicia," said Martínez Costas. The primary concern is that infected animals are asymptomatic, making detection challenging. Moreover, transmission is not limited to tick bites; contact with infected fluids can also spread the virus.
The work at CiQUS represents a significant step toward addressing this lethal and emerging disease. In July 2024, shortly after the virus's circulation in Galicia was confirmed, the seventh fatality was recorded—an elderly man who died in Madrid after contracting the virus in Toledo. Experts consider the virus's circulation in Galicia to be low, but the scientific community is actively working to halt its spread.
By Laura Filloy, Gciencia.
>O grupo de Viroloxía Molecular no CiQUS