Circular CCR5 peptide conjugates and uses thereof (WO2008074895)

Abstract

Background: Several new strategies targeting HIV infection aim to inhibit virus entry by blocking the chemokine receptor CCR5 used by macrophage tropic strains associated with early infection. The current application uses virus-like particles as a support to present CCR5 peptide antigens. Objectives: The virus-like particle (VLP)–CCR5 composition aims to function as either a preventative and/or therapeutic vaccine inducing durable autoantibodies that can block CCR5 and prevent HIV entry or attenuate disease progression. Methods: The novelty of the current application lies in the chemical conjugation of circularised peptide antigens to VLPs, primarily the CCR5 N-terminal domain alone but also including the first extracellular loop (ECL-1). Immunised mice and rabbits generated antibodies that recognised native CCR5 and inhibited entry of pseudotype viruses bearing envelope glycoproteins from diverse primary strains in vitro. Results/conclusions: Further work is required to assess the in vivo therapeutic potential of these CCR5 compositions. As therapeutic vaccines and/or preventative vaccines, the potential for selecting CXCR4 tropic virus populations associated with disease progression will need to be considered in addition to the broader consequences of targeting a cellular antigen involved in innate immunity.