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

Science. 2019 Feb 8;363(6427):649-654. doi: 10.1126/science.aat9120. Epub 2018 Dec 20.


In vaccine design, antigens are often arrayed in a multivalent nanoparticle form, but in vivo mechanisms underlying the enhanced immunity elicited by such vaccines remain poorly understood. We compared the fates of two different heavily glycosylated HIV antigens, a gp120-derived mini-protein and a large, stabilized envelope trimer, in protein nanoparticle or "free" forms after 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 affected 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology*
  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibody Formation*
  • Complement Fixation Tests
  • Complement System Proteins / immunology
  • Dendritic Cells / immunology
  • Female
  • Germinal Center / immunology*
  • HIV Antibodies / immunology
  • HIV Envelope Protein gp120 / immunology*
  • HIV Infections / immunology*
  • HIV Infections / prevention & control
  • Immunity, Innate*
  • Liposomes
  • Mannose-Binding Lectin / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Multiprotein Complexes
  • Nanoparticles
  • Polysaccharides / immunology*
  • Receptors, Complement / immunology


  • AIDS Vaccines
  • Antibodies, Neutralizing
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Liposomes
  • Mannose-Binding Lectin
  • Multiprotein Complexes
  • Polysaccharides
  • Receptors, Complement
  • Complement System Proteins