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Project C4: Alexander Müller, doctoral researcher (MD)

Human herpesvirus-8, also known as Kaposi`s sarcoma-associated Herpesvirus (KSHV), is responsible for approximately 45,000 new cases of Kaposi`s sarcoma, a malignant cancer, each year. This mainly affects immunocompromised people, such as HIV patients. Currently, there is no way to prevent this disease, so the development of a vaccine for active immunization is of great importance for individuals at risk.

Therefore, the aim is to use the KSHV viral glycoproteins gH/gL as a target to produce clinically effective active immunization. Different approaches comprising monomeric, dimeric and trimeric gH/gL combined with various adjuvants will be used to immunize mice and their sera subsequently tested in cell cultures for their neutralizing activity in vitro.

KSHV is a species-specific virus that affects only humans. It can enter murine cells, but lytic replication is not possible.

Hence, to evaluate its efficacy in vivo, a model system is needed that takes advantage of KSHV's close relationship to Murine Gamma Herpesvirus 68. It is known that binding of KSHV to the receptor EphA2 is critical for its cell tropism. Therefore, the binding properties of MHV-68 to Eph receptors will be analyzed to draw conclusions on the usefulness of MHV-68 as a model system for in vivo testing of immunization strategies against KSHV.

The results obtained in this project thus form the basis for the next step in the development of a successful vaccination strategy - the evaluation of effectiveness in living organisms, which is bringing us closer towards an effective vaccination strategy for humans.