Mannose-Binding Lectin and Complement Mediate Follicular Localization and Enhanced Immunogenicity of Diverse Protein Nanoparticle Immunogens

Abstract

Nanoparticle (NP) vaccine formulations promote immune responses through multiple mechanisms. We recently reported that mannose-binding lectin (MBL) triggers trafficking of glycosylated HIV Env-immunogen NPs to lymph node follicles. Here, we investigated effects of MBL and complement on NP forms of HIV and other clinically-relevant antigens. MBL recognition of oligomannose on gp120 nanoparticles significantly increased antigen accumulation in lymph nodes and antigen-specific germinal center (GC) responses. MBL and complement also mediated follicular trafficking and enhanced GC responses to influenza, HBV, and HPV particulate antigens. Using model protein nanoparticles bearing titrated levels of glycosylation, we determined that mannose patches at a minimal density of 2.1x10-3 mannose patches/nm2 were required to trigger follicular targeting, which increased with increasing glycan density up to at least ~8.2×10-3 mannose patches/nm2. Thus, innate immune recognition of glycans has a significant impact on humoral immunity, and these findings provide a framework for engineering glycan recognition to optimize vaccine efficacy.