Periodic Reporting for period 6 - CCHFVaccine (Crimean-Congo Haemorrhagic Fever Vaccine)
Reporting period: 2024-01-01 to 2025-09-30
Crimean-Congo haemorrhagic fever virus (CCHFV) is a long neglected but rapidly emerging pathogen, responsible for severe disease and often fatal outbreaks. Recent fatal human cases in Portugal and Greece, together with the established presence of CCHFV in France, underscore that this is no longer a distant threat but an escalating public health concern within Europe itself.
The virus is primarily transmitted via tick bites, but also through handling of infected livestock or treatment of CCHFV infected patients. In humans, CCHFV cause febrile-illness, which in some cases are mild, but in other cause sever diseases with hemorrhagic manifestations. The fatality rate range between 5-30% and currently there are no approved treatment or vaccine against CCHF. The extensive spread of the virus, mode of transmission and severity of the disease make CCHF a significant threat to the global health and the World Health Organization (WHO) recently put CCHFV on its blue print list to emphasis the importance of developing antivirals and/or a vaccine (project https://www.who.int/blueprint/(opens in new window)).
The major goal of CCHFVaccine project is to develop a vaccine candidate, which can be specifically used to protect high risks groups in endemic area such as health care workers, farmers, slaughter houses, tourists, and others. This vaccine will not only protect these at-risk populations but will also contribute to limit the transmission of the virus in endemic regions and neighboring areas. CCHFVaccine project will build a unique biobank, which will be used to define biomarkers and also signature for protective immunity against this disease.
The virus is primarily transmitted via tick bites, but also through handling of infected livestock or treatment of CCHFV infected patients. In humans, CCHFV cause febrile-illness, which in some cases are mild, but in other cause sever diseases with hemorrhagic manifestations. The fatality rate range between 5-30% and currently there are no approved treatment or vaccine against CCHF. The extensive spread of the virus, mode of transmission and severity of the disease make CCHF a significant threat to the global health and the World Health Organization (WHO) recently put CCHFV on its blue print list to emphasis the importance of developing antivirals and/or a vaccine (project https://www.who.int/blueprint/(opens in new window)).
The major goal of CCHFVaccine project is to develop a vaccine candidate, which can be specifically used to protect high risks groups in endemic area such as health care workers, farmers, slaughter houses, tourists, and others. This vaccine will not only protect these at-risk populations but will also contribute to limit the transmission of the virus in endemic regions and neighboring areas. CCHFVaccine project will build a unique biobank, which will be used to define biomarkers and also signature for protective immunity against this disease.
The CCHFVaccine programme has delivered a major advance in this field by establishing the first sheep animal model for CCHFV, a critical breakthrough for understanding virus transmission and evaluating intervention strategies. Using this novel and highly relevant model, we have successfully tested vaccine candidates. Additionally, our research on non-human primates exhibited significant protection against CCHFV, highlighting the crucial role of the N plasmid in providing protection.
CCHFVaccine has also successfully generated multiple human vaccine candidates using two complementary and advanced platforms: DNA-based and mRNA-based vaccines, positioning the field for rapid clinical translation and improved preparedness against future outbreaks. Furthermore, a Phase I clinical trial to Evaluate Safety and Immunogenicity of DNA Vaccine N-pVAX1 against Crimean Congo Hemorrhagic Fever was conducted. The trial started in November 2024, with final vaccination conducted in December 2025. The final 3-month follow-up samples for the highest-dose cohort are pending and will be collected in February 2026. Comprehensive data analysis is actively ongoing, while the preparation of the Clinical Study Report (CSR) has already commenced. Preliminary data from a first analysis of the antibody response to CCHF N protein suggests a clear dose response in the study.
The Final CCHFVaccine Symposium in December 2024 included a roundtable discussion on Strategic Advancements and Challenges in Implementing a DNA Vaccine for CCF Virus. This roundtable included participation from the World Health Organisation (WHO), the European Medicines Agency (EMA) and the French National Agency for Health Security (ANSES), as well as CCHFVaccine partners NCIPD and KI.
CCHFVaccine has also successfully generated multiple human vaccine candidates using two complementary and advanced platforms: DNA-based and mRNA-based vaccines, positioning the field for rapid clinical translation and improved preparedness against future outbreaks. Furthermore, a Phase I clinical trial to Evaluate Safety and Immunogenicity of DNA Vaccine N-pVAX1 against Crimean Congo Hemorrhagic Fever was conducted. The trial started in November 2024, with final vaccination conducted in December 2025. The final 3-month follow-up samples for the highest-dose cohort are pending and will be collected in February 2026. Comprehensive data analysis is actively ongoing, while the preparation of the Clinical Study Report (CSR) has already commenced. Preliminary data from a first analysis of the antibody response to CCHF N protein suggests a clear dose response in the study.
The Final CCHFVaccine Symposium in December 2024 included a roundtable discussion on Strategic Advancements and Challenges in Implementing a DNA Vaccine for CCF Virus. This roundtable included participation from the World Health Organisation (WHO), the European Medicines Agency (EMA) and the French National Agency for Health Security (ANSES), as well as CCHFVaccine partners NCIPD and KI.
The CCHFV patient sample Biobank has played a crucial role in generating datasets on adaptive immune and omic responses to CCHFV, offering insights that could significantly contribute to the development of life-saving vaccines and therapeutics. Several compelling research reports are in the pipeline for publication.
Moreover, our collaborative efforts have facilitated the establishment of fruitful relationships with CCHF-endemic countries, including not only Turkey and Tajikistan but also South Africa and India. Interactions with leading Biotech companies, such as Pfizer, Astra, and Biontech, have been initiated, positioning us as a valuable resource in the ongoing fight against CCHF.
The CCHFVaccine programme established the first sheep animal model for CCHFV and subsequently tested vaccine candidates using this model. In parallel, the programme has developed tools, methodologies, and scalable vaccination strategies for domestic animals in endemic and neighbouring regions. By targeting the animal reservoir, these efforts have the potential to markedly reduce viral circulation and strengthen disease control in Europe and globally. This progress provides strong momentum and tangible hope that effective vaccination strategies against CCHFV are within reach.
The project has successfully generated multiple human vaccine candidates using two complementary and advanced platforms: DNA-based and mRNA-based vaccines, positioning the field for rapid clinical translation and improved preparedness against future outbreaks. Furthermore, a Phase I clinical trial to Evaluate Safety and Immunogenicity of DNA Vaccine N-pVAX1 against Crimean Congo Hemorrhagic Fever was conducted.
In addition to the activities outlined above, training workshops and exchange programmes have empowered scientists with advanced skills, harmonised SOPs, and hands-on experience, enabling rapid implementation of cutting-edge techniques across participating laboratories. This strong commitment to capacity building, combined with the multidisciplinary approach at the core of CCHFVaccine, is firmly grounded in a public health–driven rationale and ensures that scientific advances translate into sustainable impact, preparedness, and long-term benefit.
A defining strength of CCHFVaccine has been its integrative and collaborative approach. By building on, aligning with, and complementing other nationally and internationally funded projects—particularly European Commission–supported initiatives—the programme created strong synergies, avoided duplication, and accelerated progress toward shared public health goals. This coordinated framework has maximized impact, strengthened preparedness, and ensured that CCHFVaccine outcomes are embedded within the broader European and global response to emerging viral threats.
Moreover, our collaborative efforts have facilitated the establishment of fruitful relationships with CCHF-endemic countries, including not only Turkey and Tajikistan but also South Africa and India. Interactions with leading Biotech companies, such as Pfizer, Astra, and Biontech, have been initiated, positioning us as a valuable resource in the ongoing fight against CCHF.
The CCHFVaccine programme established the first sheep animal model for CCHFV and subsequently tested vaccine candidates using this model. In parallel, the programme has developed tools, methodologies, and scalable vaccination strategies for domestic animals in endemic and neighbouring regions. By targeting the animal reservoir, these efforts have the potential to markedly reduce viral circulation and strengthen disease control in Europe and globally. This progress provides strong momentum and tangible hope that effective vaccination strategies against CCHFV are within reach.
The project has successfully generated multiple human vaccine candidates using two complementary and advanced platforms: DNA-based and mRNA-based vaccines, positioning the field for rapid clinical translation and improved preparedness against future outbreaks. Furthermore, a Phase I clinical trial to Evaluate Safety and Immunogenicity of DNA Vaccine N-pVAX1 against Crimean Congo Hemorrhagic Fever was conducted.
In addition to the activities outlined above, training workshops and exchange programmes have empowered scientists with advanced skills, harmonised SOPs, and hands-on experience, enabling rapid implementation of cutting-edge techniques across participating laboratories. This strong commitment to capacity building, combined with the multidisciplinary approach at the core of CCHFVaccine, is firmly grounded in a public health–driven rationale and ensures that scientific advances translate into sustainable impact, preparedness, and long-term benefit.
A defining strength of CCHFVaccine has been its integrative and collaborative approach. By building on, aligning with, and complementing other nationally and internationally funded projects—particularly European Commission–supported initiatives—the programme created strong synergies, avoided duplication, and accelerated progress toward shared public health goals. This coordinated framework has maximized impact, strengthened preparedness, and ensured that CCHFVaccine outcomes are embedded within the broader European and global response to emerging viral threats.