Protein and Glycan Mimicry in HIV Vaccine Design

Antigenic mimicry is a fundamental tenet of structure-based vaccinology. Vaccine strategies for the human immunodeficiency virus type 1 (HIV-1) focus on the mimicry of its envelope spike (Env) due to its exposed location on the viral membrane and role in mediating infection. However, the virus has evolved to minimize the immunogenicity of conserved epitopes on the envelope spike. This principle is starkly illustrated by the presence of an extensive array of host-derived glycans, which act to shield the underlying protein from antibody recognition. Despite these hurdles, a subset of HIV-infected individuals eventually develop broadly neutralizing antibodies that recognize these virally presented glycans. Effective HIV-1 immunogens are therefore likely to involve some degree of mimicry of both the protein and glycan components of Env. As such, considerable efforts have been made to characterize the structure of the envelope spike and its glycan shield. This review summarizes the recent progress made in this field, with an emphasis on our growing understanding of the factors shaping the glycan shield of Env derived from both virus and soluble immunogens. We argue that recombinant mimics of the envelope spike are currently capable of capturing many features of the native viral glycan shield. Finally, we explore strategies through which the immunogenicity of Env glycans may be enhanced in the development of future immunogens.