Isebois, E; Veillette, M; Dion-Dupont, V; Lavoie, J; Corbeil, J; Culley, A; Duchaine, C; Georgiev, IS; Joyce, MG; Chen, RE; Leung, K; Mckee, K; Druz, A; Van Galen, JG; Kanekiyo, M; Tsybovsky, Y; Yang, E; Yang, Y; Acharya, P; Pancera, M; Thomas, PV; Wanninger, T; Yassine, HM; Baxa, U; Doria-Rose, NA; Cheng, C; Graham, BS; Mascola, , JR; Kwong, PD
Antigen multimerization on a nanoparticle can result in improved neutralizing antibody responses. A platform that has been successfully used for displaying antigens from a number of different viruses is ferritin, a self-assembling protein nanoparticle that allows the attachment of multiple copies (24 monomers or 8 trimers) of a single antigen. Here, we design two-component ferritin variants that allow the attachment of two different antigens on a single particle in a defined ratio and geometric pattern. The two-component ferritin was specifically designed for trimeric antigens, accepting four trimers per particle for each antigen, and was tested with antigens derived from HIV-1 envelope (Env) and influenza hemagglutinin (HA). Particle formation and the presence of native-like antigen conformation were confirmed through negative-stain electron microscopy and antibody-antigen binding analysis. Immunizations in guinea pigs with two-component ferritin particles, displaying diverse Env, HA, or both antigens, elicited neutralizing antibody responses against the respective viruses. The results provide proof-of-principle for the self-assembly of a two-component nanoparticle as a general technology for multimeric presentation of trimeric antigens.