Science. 2019 Feb 8; 363(6427):649-654.

PubMed ID: 30573546

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

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

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.