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Science. 2018 Dec 20. pii: eaat9120. doi: 10.1126/science.aat9120. [Epub ahead of print]

Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers.

Author information

1
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2
Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3
Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
4
International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
5
Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
6
Biological Sciences and the Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK.
7
Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
8
The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
9
International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. djirvine@mit.edu schief@scripps.edu.
10
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. djirvine@mit.edu schief@scripps.edu.
11
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
12
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
13
Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

Abstract

In vaccine design, arraying antigens in a multivalent nanoparticle form is often employed, but in vivo mechanisms underlying the enhanced immunity elicited by such vaccines remain poorly understood. Here we compared the fate of two different heavily glycosylated HIV antigens, a gp120-derived mini-protein and a large, stabilized envelope trimer, in protein nanoparticle or "free" forms following primary immunization. Unlike monomeric antigens, nanoparticles were rapidly shuttled to the follicular dendritic cell (FDC) network and then concentrated in germinal centers in a complement-, mannose-binding lectin (MBL)-, and immunogen glycan-dependent manner. Loss of FDC localization in MBL-deficient mice or via immunogen deglycosylation significantly impacted antibody responses. These findings identify an innate immune-mediated recognition pathway promoting antibody responses to particulate antigens, with broad implications for humoral immunity and vaccine design.

PMID:
30573546
DOI:
10.1126/science.aat9120

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