 A successful HIV vaccine should elicit broad adaptive and innate immune responses through prime boost platforms which are influenced by various factors such as antigen selection, vector type, delivery route, dose, adjuvant, boosting regimen, order of vector injection, and intervals between vaccinations. Heterologous may be better than homologous prime boost regimens for protection, with the most advanced strategies using canarypox or adenovirus vectors expressing mosaic antigens boosted by GP140 protein. DNA prime and vector protein boost regimens are at a less advanced stage of development but could contribute substantially to HIV epidemic control as part of a comprehensive prevention program. Post-efficacy activities are necessary for pumped vaccine access in populations with the greatest need. This article was authored by Jean-Louis Excler and Jerome H. Kim.