Abstract
Although vaccines have been successfully developed against several pathogens, designing an effective vaccine to protect against human immunodeficiency virus (HIV) has remained an intractable challenge. To address this, the research community has looked to human and non-human primate studies to understand the correlates of protective immunity, based on which a targeted vaccine strategy may be designed. Two distinct approaches, focused on different immune correlates of protection, have emerged. The first focuses on structure-based design of HIV envelope immunogens that are able to induce antibodies that neutralize the virus. The second focuses on strategies aimed at driving non-neutralizing polyclonal and polyfunctional antibodies that engage other arms of immunity to clear the virus. Here we review these two different vaccine design strategies and posit that ultimately the convergence of these two efforts will likely be necessary for the development of a globally protective HIV vaccine.