Mannose-binding lectin and complement mediate follicular localization and enhanced immunogenicity of diverse protein nanoparticle immunogens
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1-s2.0-S2211124721017216-main.pdf
Description
Published version
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3.7 MB
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Checksum (MD5)
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Author(s)
Read, Benjamin J
Won, Lori
Kraft, John C
Sappington, Isaac
Aung, Aereas
Wu, Shengwei
Bals, Julia
Chen, Chengbo
Lee, Kelly K
Lingwood, Daniel
Date Issued
2022
Journal
Cell Reports
Publisher
Elsevier BV
Citation
Read, Benjamin J, Won, Lori, Kraft, John C, Sappington, Isaac, Aung, Aereas et al. 2022. "Mannose-binding lectin and complement mediate follicular localization and enhanced immunogenicity of diverse protein nanoparticle immunogens." Cell Reports, 38 (2).
Version
Final published version
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 investigate effects of MBL and complement on NP forms of HIV and other viral antigens. MBL recognition of oligomannose on gp120 nanoparticles significantly increases antigen accumulation in lymph nodes and antigen-specific germinal center (GC) responses. MBL and complement also mediate follicular trafficking and enhance GC responses to influenza, HBV, and HPV particulate antigens. Using model protein nanoparticles bearing titrated levels of glycosylation, we determine that mannose patches at a minimal density of 2.1 × 10-3 mannose patches/nm2 are required to trigger follicular targeting, which increases with increasing glycan density up to at least ∼8.2 × 10-3 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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1016/J.CELREP.2021.110217
