Interview with Sotiris Missaildis, ACT-CHIK Coordinator

By Kelly Prifti, Project Manager 

Dr. Sotiris Missailidis, Head of Vaccine Innovation Development at the DARRI, manages the vaccine portfolio of the Institute Pasteur and leads the Innovation development of vaccine projects from basic research to clinical development, spin-off activities and industrial partnerships for vaccine-related projects. Sotiris joined Institut Pasteur in 2024, having previously held the position for seven years of Director of Technological Development and Innovation at Bio-Manguinhos Institute of Technology in Immunobiologics at the Fiocruz Foundation in Brazil. 

Sotiris brings more than 30 years of experience in applied research focused on the development of vaccines, therapeutic and diagnostic applications. He is a trained Biologist, with MSc and DPhil in Chemistry from the University of York and post-doctoral studies in Pharmaceutical Sciences (Nottingham) and Molecular biology (Cambridge) in the UK. He was an academic at the Open University, UK, visiting professor at the Universities of Lisbon (Portugal) and Paris (France), as well as UFRJ and UERJ in Brazil and EACR fellow at the University of Patras (Greece). He was founder and director of Euzoia Ltd (UK) and Naxos DNA Services (Brazil) and Senior Researcher at the Oswaldo Cruz Institute (IOC) and Bio-Manguinhos at Fiocruz, before he joined the Institut Pasteur. 

Dr. Missailidis, tell us about the history of the ACT-CHIK project 

The ACT-CHIK project has been 15 years in the making. It began with research led by Frédéric Tangy in 2011, in which genes coding for selected antigens from the chikungunya virus were inserted into the genome of the well-established measles virus Schwarz vaccine strain to develop a live-attenuated, recombinant vaccine for chikungunya, among others. By delivering the chikungunya antigens directly to macrophages and dendritic cells - the most potent and effective antigen-presenting cells – a specific immune response to chikungunya virus is triggered. This results in a powerful, antigen-focused immune response, which is most likely to confer long-term immunity as do measles vaccine.

Following this research, Institut Pasteur teamed up with Themis Bioscience (“Themis”) and in collaboration with the Department of Clinical Pharmacology at the Medical University of Vienna and the Viral Diseases Branch of the Walter Reed Army Institute of Research (WRAIR) in the USA, conducted a first-in-man Phase I clinical trial in Austria which showed good immunogenicity, safety and tolerability.  

Five other Phase I and II clinical trials followed in Europe and the United States, including Puerto Rico (where chikungunya is endemic). In total, approximately 600 adult participants were included in the six trials, demonstrating satisfactory safety, tolerability, and immunogenicity profiles. 

Funding from CEPI allowed for the development of a Phase III vaccine drug substance.  However, In 2020, Merck acquired Themis and halted development of the MV-CHIK candidate. The drug substance was returned to Institut Pasteur along with all relevant documentation. When the EDCTP3 call for proposals “Accelerating the development of prophylactic vaccines against Neglected Tropical Diseases (NTDs) in sub-Saharan Africa” was launched, the idea for the ACT-CHIK project took shape. 

ACT-CHIK will conduct a Phase Ib/III multicentric, international clinical trial to evaluate the safety and immunogenicity of MV-CHIK in adults (18–55 years), adolescents (12–17 years), and children (5–11 years) living in Rwanda, Kenya, Nigeria, and Senegal. By enrolling 940 participants across both endemic and non-endemic areas, the trial will generate essential data to advance the clinical development plan for African populations, including younger age groups. 

What makes the development of vaccines for neglected tropical diseases such as Chikungunya so challenging? 

The development of vaccines for neglected tropical diseases, such as Chik, is very challenging for a number of reasons. First of all, Chik is often misdiagnosed for other arboviral diseases, including Dengue or Zika, but also for malaria in Africa, which makes the disease under-reported and its importance for public health often masked. Furthermore, these diseases are not of particular interest to the large pharmaceutical and vaccine industries, as the market remains limited. They are important diseases that affect millions, and in the case of Chik have significant debilitating effects on the patients and financial losses to the countries affected, mainly due to inability of the individual to return to the workforce and the need of medical treatment and often hospitalization. However, as ChikV is not life threatening, and affects LMICs but is not in the GAVI list or other humanitarian organizations, it does not have a guaranteed market available.  Thus, the funding for the development of vaccines for ChikV and other neglected tropical diseases remains low and limited to a few funding bodies, and the potential for subsequent commercialization of the vaccine, so that it reaches endemic countries where it is mostly needed, remains difficult. This is another important aspect of the ACT-CHIK project. It includes two producers, one in Africa and one in Latin America, that at the end of the project would have the capacity to register, commercialize and produce the vaccine exactly at such endemic regions, where the two existing vaccines are not used.  

What is your vision for the future of vaccine innovation at Institut Pasteur, and how does this project contribute to that? 

The future of vaccine innovation at Institut Pasteur is very promising. We are at the crossroads, in a moment where vaccines and vaccine research are criticized in certain parts of the world and public perception is inevitably affected, but exactly when the IP is advancing a number of vaccine projects through its pipeline to the clinic, contributing significantly to combating neglected or public health related diseases worldwide. The ACT-CHIK project, specifically, is a flagship in this effort, as it aspires to be the first IP developed vaccine, from research to commercialization in the last 45 years, since the HBV vaccine commercialized in 1981. However, vaccine innovation and development at the institute is not based on a single product, as our MOPEVAC-Lassa and our synthetic oligosaccharide Quadrivalent Shigella vaccines are both in early stages of clinical development in France and Africa respectively. Furthermore, an mRNA vaccine for malaria is currently under development aiming to reach the clinic soon after and a large number of other vaccines in earlier stages of preclinical development, are contributing to a healthy pipeline of vaccine innovation in the institute, that covers different platforms and diseases and goes from early research to clinical development and eventually to the market. This has also been recognized nationally and internationally with the participation of the institute in the European Vaccine Hub (EVH), the France Vaccins program in France and the Vaccine Manufacturing Initiative (VMI) within the Pasteur Network.