HIV vaccine development at the turn of the 21st centuryGirard, Marc P.a; Plotkin, Stanley A.bCurrent Opinion in HIV and AIDS: January 2012 - Volume 7 - Issue 1 - p 4–9 doi: 10.1097/COH.0b013e32834ddc96 SYSTEMS BIOLOGY IN UNDERSTANDING HIV PATHOGENESIS AND GUIDING VACCINE DEVELOPMENT: Edited by Rafick-Pierre Sékaly and Bali Pulendran Abstract Author Information Purpose of review To review the status of HIV vaccine development Recent findings Since the discovery of HIV-1 in the early 1980s considerable effort has been exerted to develop a prophylactic vaccine, with relatively meagre results. The absence of natural immunity has proven to be a major stumbling block in identifying a mechanism of protection. However, many different animal models have contributed to our knowledge of the pathogenesis of infection and of the variety of antibody and cellular responses that are induced by the virus. The knowledge created by the studies in nonhuman primates, although important, has not necessarily been proven applicable in humans and thus an effective vaccine has been elusive. The combined lack of a fully predictive animal model (‘mice lie and monkeys exaggerate’) and lack of defined markers of immune protection against HIV-1 necessitate that HIV vaccines be tested directly for efficacy in phase IIb/III efficacy trials in human volunteers at risk. A trial conducted in Thailand showed moderate but significant protection against infection. Summary The process of HIV vaccine development is slow, costly and tedious. However, recent preclinical and clinical results have fortunately been a source of renewed optimism in the field. aFrench National Academy of Medicine, Lyon, France bUniversity of Pennsylvania, Philadelphia, Pennsylvania, USA Correspondence to Dr Stanley A. Plotkin, 4650 Wismer Road, Doylestown, PA 18902, USA. Tel: +1 215 297 9321; fax: +1 215 297 9323; e-mail: firstname.lastname@example.org © 2012 Lippincott Williams & Wilkins, Inc.