Therapeutic antibodies against poxviruses European project starts with preclinical and clinical development

In addition to the eradicated “human” smallpox (Orthopoxvirus variolae), which can only infect humans, there are other poxviruses. These include, for example, Mpox (“monkeypox,” Orthopoxvirus monkeypox), which can be transmitted from person to person, but also from animals to humans. The traditional smallpox vaccine also protects against Mpox. However, with the eradication of smallpox, routine smallpox vaccination was discontinued—with the result that younger people in particular are not vaccinated today. This is where the THANATOS project comes in, which is funded by the EU with 13.5 million euros.

The THANATOS project is developing an antibody-based therapeutic, designed to neutralize the smallpox and Mpox (monkeypox) viruses. It will first be tested in preclinical studies, followed by clinical trials in humans. The starting point is an antibody isolated from macaques by the Institut de Recherche Biomédicale des Armées (IRBA) in France in cooperation with the Department of Medical Biotechnology at TU Braunschweig.

The role of TU Braunschweig in the current project is to humanize and perform biochemical analysis of this antibody, as well as to produce the antibodies for in vitro and in vivo experiments. In Braunschweig, Dr. Maren Schubert from the Helmholtz Center for Infection Research (HZI) is also involved in the project and will prepare the surface proteins of smallpox viruses as well as non-infectious virus-like particles (VLPs) for antibody analysis and quality control of the therapeutic antibody. Following the humanization and biochemical analysis of the antibody, its efficacy against cowpox and Mpox will be validated in experiments, followed by the preclinical development.

This includes, among other things, the antibody’s behavior in the body, potential toxic effects, possible cross-reactions, the development of a cell line for production, and GMP (Good Manufacturing Practice) production for the Phase 1 clinical trial. The clinical Phase 1, in which the safety of the therapeutic agent in humans is evaluated, is the endpoint of this project. At the same time, preparations are underway for a potential Phase 2 clinical trial (efficacy) to evaluate the drug’s effectiveness in treating Mpox.

“Developing a therapeutic agent for use in humans is a challenging and highly responsible task. We are excited to take on this project and thank the EU for funding not only research projects but also development projects,” says Dianne Gnann, a researcher in the Department of Medical Biotechnology.

Professor Michael Hust adds: “We have many years of experience in developing antibodies against viral pathogens, including their translation into the clinic. This project is a milestone in the development of a therapeutic agent against various poxviruses.”

Contributing partners

Partner in the THANATOS (Therapeutic antibodies neutralizing all the orthopoxvirus infectious for humans, including smallpox) project are: Commissariat a l’energie atomique et aux energies alternatives (CEA, France), Technische Universität Braunschweig (Germany), Institut de Recherche Biomédicale des Armées (IRBA, France), MabSilico (France), Helmholtz-Zentrum für Infektionsforschung (HZI, Germany), InnovationActa (Italy), NorthX Biologicals (Sweden), Eurofins Optimed (France), Centre Pasteur Cameroon (Cameroon), BSL Bioservice (Germany).