FOR-COVID

Bavarian consortium for research on the pandemic disease COVID-19 (FOR-COVID)

T cell antigens for new multivalent vector vaccines against SARS-CoV-2-like coronaviruses

Projectleader
Dr. Alina Tscherne
Prof. Dr. Gerd Sutter

The SARS-CoV-2 spike (S) glycoprotein serves as the key antigen in all COVID-19 vaccines
including those already licensed and many others still undergoing clinical development. The
S antigen at the virion surface is the target of SARS-CoV-2 neutralizing antibodies, and the
receptor-binding domain (RBD) of S is recognized by >90% of neutralizing antibodies elicited
upon SARS-CoV-2 infection. While, in a very simplified view, neutralizing antibodies predominantly stop the infection of cells with extracellular virus, CD8+ T cells are mostly needed to clear an already ongoing infection inside the cells or the organism. Thus, T cellbased vaccines offer an attractive alternative to complement the protective immunity provided by vaccine induced antibodies. SARS-CoV-2-specific CD8+ T cells recognize a broad range of epitopes.. Here, we will investigate additional viral antigens to serve as candidates for the development of SARS-CoV-2-specific  T cell vaccines. For antigen delivery, we will use vector vaccines based on recombinant Modified Vaccinia virus Ankara (MVA), a safety-tested vaccinia virus highly suitable for clinical evaluations of multivalent candidate vaccines against infectious diseases and cancer. One focus will be the evaluation of the SARS-CoV-2 nucleocapsid protein, the membrane protein and the ORF3a accessory protein, which we selected on the basis of our results from SARS-CoV-2 target gene screening and antigenicity testing during the ongoing funding period. In addition, we will design and investigate synthetic gene sequences encoding artificial polyepitope-antigens. All T cell target antigens will be delivered by MVA vector vaccines. The project will use established preclinical models for MVA vector vaccine characterization to test immunogenicity and protective efficacy of the T cell vector vaccines alone and in comparison/addition to immunizations with the already well characterized S-specific MSarsCoV-2 vector vaccine.
Overall objective is to investigate the feasibility of generating more broadly effective multivalent MVA vector vaccines against SARS-CoV-2. The project will contribute to the starting efforts of enhanced post-pandemic preparedness against newly emerging sarbecoviruses and related beta-coronaviruses.

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