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Dr. rer. nat. Ralf Amann

Research projects:


Despite the unquestionable need for effective vaccines, it remains the challenge of developing customized vaccines in a quick and cost-effective way for both the fields of oncology and infectious diseases. Currently, neither is possible using traditional vaccine platforms due to excessive development times and costs of genuinely individualized vaccines, or insufficient immune responses.

Utilizing the modular design of the Orf virus platform technology, highly effective mono- or multivalent vaccines against infectious diseases and cancer can be generated in a cost- and time-efficient manner. Importantly, the application of the preventive and therapeutic vaccines results in balanced B- and T-cell immune responses without the need for any additional adjuvants or the necessity of viral vector multiplication. Due to a lack of neutralizing antibodies targeting the Orf virus (ORFV), multiple immunizations using our technology can be performed easily without any loss in efficacy.

The design of our vaccine vectors comprise tumor- or pathogen-specific antigens (NEO), as well as accessory transgenes encoding for molecules or immunostimulatory elements (ME). Due to the development of an effecive selection system, these highly potent and safe vaccines can be available within few weeks.

Therefore, generation of ORFV recombinants, which express different foreign genes (antigens), could be demonstrated to protect against lethal challenge infection with Herpesvirus (Herpes Suid 1), Borna disease Virus, Pestivirus (CSFV), Influenza virus (HPAIV H5N1), Rabies virus or Calicivirus (RHDV) not only in animal models, but also in natural hosts. Recently, our group advanced a highly effective multivalent SARS-CoV-2 vaccine to the clinics. Notably, ORFV recombinant replication is not needed to mediate protective immunity.

Innovative strategies to improve selection and generation of new, multivalent ORFV recombinants are under development. Moreover, important unravelled questions remain to be solved concerning the unique immunostimulating properties of ORFV to activate innate and long-lasting adaptive (balanced Th1 and Th2 type response) immunity. Therefore, projects and fields of interest include:

• Inducing mucosal immunity by novel vaccine concepts
• Enhancing vaccine efficacy by triggering innate immune signaling of Dendritic Cells
• Identification of synergistic vaccine technologies to maximize vaccine efficacy by heterologous vaccination regimens
• Enhancing vaccine-mediated humoral immune responses
• Maximizing cellular immunity for effective therapies against chronic infections and cancer
• Investigating the ORFV-induced stimulation of the human immune system
• Continuous improvement of the generation and selection of new, multivalent ORFV recombinants
• Enhancement and fine-tuning of foreign gene expression in ORFV
• Development of procedures appropriate for large scale vaccine production

Since it is described in the literature that the species of ORFV also includes strains with excellent oncolytic properties, our group more recently engaged in the development of an ORFV based oncolytic virus (OV) platform technology (see figure A). We have identified key features of the vaccine platform that can be transferred to the development of OVs, which include (i) the possibility of multiple administration due to the lack ORFV-neutralizing antibodies, (ii) tolerability, (iii) an excellent safety profile due to the narrow host spectrum and the lack of systemic spread, (iv) genetic stability, (v) the option of inserting transgenes in a stable manner and (vi) a GMP-compliant manufacturing process. Thus, we have developed an ORFV with excellent lytic properties for oncolytic virotherapy via comparison of different ORFV wild-type isolates and reverse genetics. Further, we were able to show that this prototype can be genetically modified and that transgenes can be stably integrated. This allows the "arming" of our OV with anti-tumor transgenes such as immunomodulators, chemoattractors or checkpoint antibodies in order to intensify the oncolytic effects and to modulate the tumor microenvironment in such a way that the effectiveness of complementary (immune-) therapies is improved (see figure B).

Mechanism of action of oncolytic ORFV. Oncolytic virus (OV) is taken up by healthy cells and tumor cells, replicating exclusively in and destroying tumor cells. As a result of tumor lysis, new OVs are released, which in turn can infect and destroy other tumor cells. In addition, a local inflammatory response is triggered and the previously immune-resistant (cold) tumor becomes susceptible (hot) to a systemic, anti-tumor immune response.

Armed oncolytic ORFVs. Transgenes can be integrated into different regions of the ORFV genome as needed, thereby expressing multiple immunomodulators such as cytokines, chemokines, costimulatory molecules, and antibodies via the oncolytic ORFV. As a result, the immunosuppressive tumor microenvironment can be destroyed, immune cells such as cytotoxic T cells can be recruited, and the anti-tumor efficiency can be increased.

Overall, our research activities aim to develop a highly adaptable viral vector platform that can target various diseases across diverse populations and environments: