HIV glycans and nanoparticle vaccines Synthetic nanoparticles have attracted widespread interest for vaccine design, but how the immune system generates a response to multimeric nanoparticles remains unclear. Tokatlian et al. studied immunity generated by HIV envelope antigens arranged in either multivalent nanoparticle forms or as single monomers (see the Perspective by Wilson). The nanoparticle HIV immunogens triggered greater antibody responses compared with the monomeric forms. Glycosylation appeared key for enhanced humoral immunity because it spurred binding to mannose-binding lectin, complement fixation, and antigen trafficking to follicular dendritic cells. The findings highlight how the innate immune system recognizes HIV nanoparticles and the importance of antigen glycosylation in the design of next-generation nano-based vaccines. Science , this issue p. 649 ; see also p. 584