Elicitation of potent SARS-CoV-2 neutralizing antibody responses through immunization using a versatile adenovirus-inspired multimerization platform

Chevillard, C; Amen, A; Besson, S; Hannani, D; Bally, I; Dettling, V; Gout, E; Moreau, CJ; Buisson, M; Gallet, S; Fenel, D; Vassal-Stermann, E; Schoehn, G; Poignard, P; Dagher, MC; Fender, P

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has shown that vaccine preparedness is critical to anticipate a fast response to emergent pathogens with high infectivity. To rapidly reach herd immunity, an affordable, easy to store and versatile vaccine platform is thus desirable. We previously designed a non-infectious adenovirus-inspired nanoparticle (ADDomer), and in the present work, we efficiently decorated this original vaccine platform with glycosylated receptor binding domain (RBD) of SARS-CoV-2. Cryo-Electron Microscopy structure revealed that up to 60 copies of this antigenic domain were bound on a single ADDomer particle with the symmetrical arrangements of a dodecahedron. Mouse immunization with the RBD decorated particles showed as early as the first immunization a significant anti-coronavirus humoral response, which was boosted after a second immunization. Neutralization assays with spike pseudo-typed-virus demonstrated the elicitation of strong neutralization titers. Remarkably, the existence of pre-existing immunity against adenoviral-derived particles enhanced the humoral response against SARS-CoV-2. This plug and play vaccine platform revisits the way of using adenovirus to combat emergent pathogens while potentially taking advantage of the adenovirus pre-immunity.