Immunoreactive Cycloimmunogen Design Based on Conformational Epitopes Derived from Human Immunodeficiency Virus Type 1 Coreceptors:Cyclic Dodecapeptides Mimic Undecapeptidyl Arches of Extracellular Loop-2 in Chemokine Receptor and Inhibit Human Immunodeficiency Virus Type 1 Infection

Shogo      Misumi; Nobutoki      Takamune; Shozo      Shoji

Abstract

Human immunodeficiency virus type 1 (HIV-1) requires a chemokine receptor (CCR5 or CXCR4) as a coreceptor not only for initiate viral entry but also protecting highly conserved neutralization epitopes from the attack of neutralizing antibodies. Over the past decade, many studies have provided new insights into the HIV entry mechanism and have focused on developing an effective vaccine strategy. However, to date, no vaccine that can provide protection from HIV-1 infection has been developed. One reason for the disappointing results has been the inability of current vaccine candidates to elicit a broadly reactive immunity to viral proteins such as the envelope (env) protein. Here, we propose that chemokine receptors are attractive targets of vaccine development because their structures are highly conserved and that our synthetic cycloimmunogens can mimic conformational-specific epitopes of undecapeptidyl arches (UPAs: R168-C178 in CCR5, N176-C186 in CXCR4) and be useful for HIV-1 novel vaccine development.

Keywords: Cycloimmunogen, HIV-1, conformational epitope, CCR5, CXCR4

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