Abstract: The present invention relates generally to soluble G protein-coupled receptor constructs. More specifically, the invention relates to soluble chemokine receptors, and soluble HIV co-receptors in particular. The invention is generally useful for designing and constructing soluble GPCR, which may be used to identify binding molecules. The invention also relates to methods of treating and/or preventing a disease or disorder associated with impaired function of such a receptor. The invention thus provides compositions and methods for therapeutic applications, such as vaccine.