A nanobody-based vaccine strategy to combat CoVID-19

SummaryThe development of a vaccine that protects against SARS-CoV-2, the coronavirus responsible for the currentpandemic (COVID-19), is urgently needed. We have developed camelid-derived antibody fragments -nanobodies - that target surface proteins on mouse and human antigen presenting cells. These targets includeclass II MHC products and the integrin alpha M (CD11b). By attaching to these nanobodies various antigens inthe form of proteins or peptides, we can elicit stronger B and T cell responses against the attached payloadswhen compared to the corresponding 'free' antigens. In particular, adducts composed of the anti-CD11bnanobody with peptides of viral origin induced a protective cytotoxic CD8 T cell response in a humanpapillomavirus model and inspire confidence that a similar outcome may be accomplished for SARS-CoV-2. Wepropose to apply these strategies to generate strong adaptive immune responses against SARS-CoV-2 antigens.The anti-mouse and anti-human class II MHC-specific nanobodies recognize all allotypes and will be used totarget antigens to mouse and human class II MHC products in normal and HLA-DR4 transgenic mice. CD4 Tcell and antibody responses will be analyzed in these studies. Adducts composed of the CD11b nanobody andCOVID-19 antigenic peptides will be used to elicit CD8 T cell responses in normal and HLA-A2 transgenic mice.For the most immunogenic SARS-CoV-2 antigens, we shall identify the minimal peptides recognized for possibleinclusion in future vaccine preparations.