Abstract
BackgroundPresenting vaccine antigens in particulate form can improve their immunogenicity by enhancing B cell activation.FindingsWe describe ferritin-based protein nanoparticles that display multiple copies of native-like HIV-1 envelope glycoprotein trimers (BG505 SOSIP.664). 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 against most tier 1A viruses, and higher responses (but not significantly), to several tier 1B viruses and the autologous tier 2 virus than when the same trimers were delivered as soluble proteins.ConclusionsThis or other nanoparticle designs may be practical ways to improve the immunogenicity of envelope glycoprotein trimers.
Highlights
Presenting vaccine antigens in particulate form can improve their immunogenicity by enhancing B cell activation
This or other nanoparticle designs may be practical ways to improve the immunogenicity of envelope glycoprotein trimers
We did observe lower affinity of gp120/gp41 interface (8ANC195, 35O22 and PGT151) and gp41 (3BC315) broadly neutralizing antibodies (bNAbs) for SOSIP.664-ferritin, which might be explained by steric hindrance of neighboring trimers on the nanoparticle (Fig. 1c)
Summary
Presenting vaccine antigens in particulate form can improve their immunogenicity by enhancing B cell activation. Findings An HIV-1 subunit vaccine should induce a broad and potent neutralizing antibody (NAb) response against the envelope glycoprotein spike (Env) [1]. Unlike other gp140 proteins, soluble, adjuvanted BG505 SOSIP.664 trimers induce NAbs against the autologous, neutralization-resistant (tier 2) virus efficiently in animals [9].
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