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Cell Rep. 2022 Jan 11;38(2):110217. doi: 10.1016/j.celrep.2021.110217.

Mannose-binding lectin and complement mediate follicular localization and enhanced immunogenicity of diverse protein nanoparticle immunogens.

Cell reports

Benjamin J Read, Lori Won, John C Kraft, Isaac Sappington, Aereas Aung, Shengwei Wu, Julia Bals, Chengbo Chen, Kelly K Lee, Daniel Lingwood, Neil P King, Darrell J Irvine

Affiliations

  1. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  2. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  3. Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  4. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  5. The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard University, Cambridge, MA 02139, USA.
  6. Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA; Biological Physics Structure and Design Program, University of Washington, Seattle, WA 98195, USA.
  7. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard University, Cambridge, MA 02139, USA; Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: [email protected].

PMID: 35021101 DOI: 10.1016/j.celrep.2021.110217

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

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Keywords: lymph node trafficking; mannose-binding lectin; nanoparticle; vaccine

Conflict of interest statement

Declaration of interests The eOD immunogens in this paper are included in patent filings from IAVI, the Scripps Research Institute, and MIT by inventors including D.J.I. N.P.K. is a co-founder, shareh

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