Targeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques

Abstract Achieving sufficient worldwide vaccination coverage against SARS-CoV-2 will require additional approaches to currently approved viral vector and mRNA vaccines. Subunit vaccines may have distinct advantages when immunizing vulnerable individuals, children pregnant women. Here, we present a new generation of subunit targeting antigens CD40-expressing antigen-presenting cells. We demonstrate that the receptor-binding domain (RBD) spike protein CD40 (αCD40.RBD) induces significant levels specific T B cells, with long-term memory phenotypes, in humanized mouse model. Additionally, single dose αCD40.RBD vaccine, injected without adjuvant, is boost rapid increase neutralizing antibodies convalescent non-human primates (NHPs) exposed six months previously SARS-CoV-2. Vaccine-elicited cross-neutralize different variants, including D614G, B1.1.7 lesser extent B1.351. Such significantly improves protection high-dose virulent challenge versus non-vaccinated animals.