D-102 Presenting native-like HIV-1 envelope trimers on ferritin nanoparticles improves their immunogenicity

Abstract

Presenting vaccine antigens in particulate form can improve their immunogenicity by enhancing B cell receptor cross-linking and B cell activation. We describe ferritin-based protein nanoparticles that display multiple copies of native-like HIV-1 envelope glycoprotein trimers (BG505 SOSIP.664) to improve upon the promising neutralizing antibody responses obtained with BG505 SOSIP.664 alone. With the aim of increasing neutralization breadth we also generated SOSIP.664-ferritin nanoparticles from different viral strains from subtypes A, B and C. Trimer- bearing nanoparticles were significantly more immunogenic than trimers in both mice and rabbits. Furthermore, rabbits immunized with the trimer- bearing nanoparticles induced significantly higher neutralizing antibody responses than when the same trimers were delivered as soluble proteins. Thus, nanoparticle-displayed native-like trimers might be valuable in the quest for an HIV-1 vaccine aimed at inducing broadly neutralizing antibodies.