Defining carbohydrate antigens as HIV vaccine candidates

The induction of high affinity antibodies capable of broad neutralization and protection against infection and/or disease is a major goal in the development of a vaccine for human immunodeficiency virus (HIV). Insights into the structure and function of the envelope (Env) protein of HIV-1 suggest that the virus is under strong selection pressure by the immune response leading to constant mutations in the Env protein including the N-glycosylation sites. Initially considered a shield against the immune system, the heavily glycosylated outer surface of the HIV Env protein has drawn attention lately as a legitimate target. The dense cluster of high mannose glycans and the great variety of complex glycans present epitopes that might impact on disease progression. Indeed a number of mannose binding proteins and at least one human anti-mannose antibody--2G12, are broadly neutralizing. Due to the low immunogenicity of carbohydrates, these targets on HIV are of limited value unless new powerful immunogens are found. One approach would be the molecular design of peptide carbohydrate mimotopes that can elicit neutralizing antibodies by recruiting optimal T cell help. Here we review existing data on carbohydrate interactions and HIV immunogenicity that serves as a basis for structural concepts and approaches used for vaccine design targeting HIV associated carbohydrate antigens. In particular, the value and the limitations of chemical (peptide libraries), structural and immunological information is illustrated.