FOR-COVID

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

Expanding immunity against SARS-CoV-2 by vaccination

Projectleaders
Prof. Dr. Ralf Wagner
Dr. David Peterhoff
Dr. Benedikt Asbach

Fortunately, highly effective and safe SARS-CoV-2 vaccines have been developed in the past 18 months. Future strategies will need to take a phenomenon referred to as “original antigenic sin” (OAS) into consideration, whereby the development of (B and T cell) immunity against pathogens/antigens is shaped by the first exposure and can hardly be expanded by closely related immunogens such as e.g. naturally emerging or vaccine-selected variants of concern (VOCs). On the far end, with regard to potential zoonotic spillovers, strategies have to be developed to bridge major structural and antigenic gaps amongst the immunogens to elicit immune responses linked to known correlates of protection. Herein we aim to explore - on the background of preexisting SARS-CoV-2 vaccine induced immunity - the potential of immunogens representing (i) naturally existing spike proteins (current SARS-CoV-2 VOCs [alpha – delta], SARS-CoV-1, WIV16, RaTG13, and MERS], (ii) ancestral or (iii) chimeric spike proteins derived from the above, or (iv) an epitope-enriched nucleoprotein-NSP3 fusion polypeptide, to augment and broaden pre-existing vaccine-induced humoral and cellmediated immunity. The proposed project will provide insight into potential limitations caused by OAS for our attempts to broaden protective immune responses, offer opportunities to overcome OAS and help to explore and potentially overcome limits regarding crossprotection beyond SARS-CoV-2 (pan-sarbecovirus or pan-betacoronavirus).

Project partners: