PMID: 30573546
Title: Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers
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.
Date: 1970-08-21
Year: 2018
Journal: Science
PMID Author: Tokatlian T, Read BJ, Jones CA, Kulp DW, Menis S, Chang JYH, Steichen JM, Kumari S, Allen JD, Dane EL, Liguori A, Sangesland M, Lingwood D, Crispin M, Schief WR, Irvine DJ
IAVI Topics: HIV Immunogen Design

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