Structural Basis for Epitopes in the gp120 Cluster A Region that Invokes Potent Effector Cell Activity

While a number of therapeutic options to control the progression of human immunodeficiency virus (HIV-1) now exist, a broadly effective preventive vaccine is still not available. Through detailed structural analysis of antibodies able to induce potent effector cell activity, a number of Env epitopes have been identified which have the potential to be considered vaccine candidates. These antibodies mainly target the gp120 Cluster A region which is only exposed upon viral binding to the target cell with epitopes becoming available for antibody binding during viral entry and fusion and, therefore, after the effective window for neutralizing antibody activity. This review will discuss recent advances in the structural characterization of these important targets with a special focus on epitopes that are involved in Fc-mediated effector function without direct viral neutralizing activities.