Dissecting the antibody constant region protective immune parameters in HIV infection

RV144 vaccine immune-correlates analysis has generated a renewed interest in understanding the potentially protective role of non-neutralizing antibodies in HIV infection and vaccine design. Antibodies consist of a variable region involved in antigen binding and a constant region. While both ends of the antibody collaborate to induce protective immunity, it is through the constant portion that an antibody provides instructions to the innate immune system on how the recognized antigen should be processed, contributing directly to antiviral immunity. Antibody constant regions, despite their name, are not uniform structures, but can vary both in protein sequence and glycosylation, together modulating antibody functionality via conformational changes that alter antibody affinity for Fc receptors, complement and so on. This review will focus on how the immune system naturally modulates the Fc domain of antibodies to achieve optimum protective Fc effector responses for vaccine and monoclonal therapeutic design efforts aimed at preventing or curing HIV infection.