Purpose of review: Advances in the understanding of the structural biology of HIV-1 proteins, and in the vulnerabilities of HIV-1 at various points in the infectious process have led to innovative approaches for vaccine constructs for clinical trials. Lessons from the successful Retrovirology study 144 (RV144) phase III Thai trial have revealed the need for novel and more potent adjuvant formulations. Fortunately, the vaccine adjuvant field is experiencing an emergence of innovative new adjuvants and strategies that may lead to improved formulations.
Recent findings: The review highlights the status of currently used and available new adjuvant formulations for HIV antigens. Adjuvants used in preclinical or in human clinical trials using HIV-1 protein antigens will be discussed along with adjuvant improvements for vectors and DNA immunization.
Summary: The HIV-1 immunogen and the design of the adjuvant formulations are both equally important for the development of an effective HIV vaccine. Adjuvants work by numerous different mechanisms, many of which are quite complex and often not well comprehended. Understanding the interplay of innate and adaptive immune responses that can be harnessed by adjuvant formulations would aid in the rational design of a well tolerated and effective vaccine formulation that can block HIV at the site of transmission.