Prof. Depfenhart's talk: Introduction to A Therapeutic DNA-launched saRNA Vaccine against Tuberculosis

Date and time: October 16^th, 2025, 10:00-10:30

Prof. Markus Depfenhart, M.D., PhD, PhD h.c., LL.M. is a German board-certified Plastic and Aesthetic Surgeon, Emergency Physician, and translational researcher based in South Africa. He is currently working as the Principle Investigator SAVAC Project North-West University and Research Prof. at NWU and WSU (in an extraordinary appointment). His transition into biotechnology is defined by a strong focus on nucleotide, protein, and peptide design, vector development, and nucleotide-based medicine, including innovative vaccine platforms. His broader research encompasses viral-free vector systems, therapeutic vaccines tailored for Africa, gene and cell therapies, antivenoms (specifically for neurotoxins) and epigenetic approaches to longevity. He serves as Principal Investigator of the SAVAC Project, advancing a therapeutic TB vaccine currently in transition to Phase I clinical testing.

Abstract:

The SAVAC Project, initiated in 2021 as a collaboration between North-West University (NWU) and Walter Sisulu University (WSU), focuses on the development of a novel DNA-launched self-amplifying RNA (saRNA) vaccine for the therapeutic treatment of tuberculosis. The approach is based on a self-developed, proprietary non-viral trans-replicon system that selectively amplifies antigen-encoding constructs at the RNA level while ensuring that no infectious virus is generated, thereby providing an additional layer of safety.

The vaccine is designed as a combination construct including SARS-CoV-2 epitopes used not for protection against SARS-CoV-2 but as immune-enhancing adjuvants. Since most individuals have been vaccinated against or exposed to SARS-CoV-2, this strategy leverages existing immune memory to boost the response to tuberculosis antigens.

Extensive in vitro studies and multiple animal models confirmed safety and efficacy. In a pivotal efficacy study, vaccinated animals showed a marked reduction of bacterial burden, with CFU counts in some cases falling below the detection limit, thereby supporting a therapeutic rather than prophylactic strategy. Another innovation is the ability to circumvent mammalian post-translational modifications, enabling more native bacterial protein expression and more effective immune responses.

The project has been funded predominantly through university resources. Over time, it has grown into a broad collaboration with the University of Pretoria, Stellenbosch University, and the University of Cape Town, with dedicated research groups now actively contributing to the program. At this conference, an overview of the vaccine construct, preclinical outcomes, and the planned transition to Phase I clinical evaluation will be presented.