A Strategy for Selectively Shielding Portions of a Peptide/Protein from Immune Response while Maintaining Immunogenicity of Contiguous Epitopes
Considerable effort is being dedicated to devise vaccination strategies to elicit a humoral response against human immunodeficiency virus (HIV). Recently we validated the fusogenic gp41 subunit of the envelope glycoprotein as a vaccine target by discovering a neutralizing antibody, D5 that inhibits HIV entry by preventing formation of the 6-helix bundle . IgG D5 binds to a highly conserved hydrophobic pocket in the groove formed by the trimeric coiled coil of the gp41 N-helices.
We designed peptides that are mimetics of the gp41 trimeric N-helix coiled coil. These chimeric peptides, such as (CCIZN17)3, comprise a designed coiled coil scaffold with a covalent stabilizing moiety and a region of the HIV N-helix sequence . Our aim is to use peptide vaccines of this class to raise D5-like antibodies that target the HIV N portion. However, when using our chimeric peptides, a substantial amount of antibodies are directed against the scaffold IZ. To circumvent this, we have...