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

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Science  20 Dec 2018:
eaat9120
DOI: 10.1126/science.aat9120

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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.

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