Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, and Australian Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Melbourne, VIC, Australia; Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Health, Central Clinical School, Monash University, Melbourne, VIC, Australia. Electronic address: [Email]
Vaccine-induced prevention of HIV infection is widely viewed as requiring both humoral and cellular immunity. Although the evidence for such a multipronged approach is not strong, this strategy increases the possibility that at least one mechanism of immunity could work to diminish new infections. The concept of broad immunity to HIV is attractive to funding bodies that seek at least some success from expensive trials. However, trying simultaneously to achieve both robust cellular and humoral immunity against HIV might be difficult. Furthermore, a multipronged approach increases the difficulty of later dissecting the immune correlates of protection and thereby iteratively improving HIV vaccines. This Viewpoint briefly discusses different approaches to tackling the challenge of inducing protective immunity to HIV and speculates on how results will move the field forward. We posit that, given the uncertain nature of immunity to HIV at present, focusing on inducing, evaluating, and optimising discrete individual mechanisms of immunity to HIV could provide the most rapid pathway to an effective HIV vaccine.