Background:  Many researchers agree that a successful HIV vaccine will include a component to elicit broadly neutralizing antibodies. However, the target of such antibodies, the envelope spike, has evolved many features to evade antibody neutralization; therefore, classical approaches to vaccine design based on simple mimicry of natural infection are unsuccessful. More promising are rational vaccine design approaches focused on understanding spike structure and the interaction of spikes with broadly neutralizing antibodies. These approaches face major challenges, particularly in translating predictable antigen behavior to predictable immunogen behavior. In addition, there are still major uncertainties about the levels of neutralizing antibody that will provide benefit against human exposure to HIV.

Conclusions:  The progress to date and challenges to be faced in developing an antibody-eliciting component of an HIV vaccine will be critically surveyed.