A Blueprint for HIV Vaccine Discovery

• Type of Material: Article
• Authors: Dennis R. Burton, Scripps Research Institute; Rafi Ahmed, Emory University; Dan H. Barouch, Beth Israel Deaconess Medical Center; Salvatore T. Butera, Scripps Research Institute; Shane Crotty, La Jolla Institute of Allergy and Immunology; Adam Godzik, Sanford Burnham Medical Research Institute; Daniel E. Kaufmann, Massachusetts Institute of Technology; M. Juliana McElrath, Fred Hutchinson Cancer Research Center; Michel C. Nussenzweig, Rockefeller University; Bali Pulendran, Emory University; Chris N. Scanlan, University of Oxford; William R. Schief, Scripps Research Institute; Guido Silvestri, Emory University; Hendrik Streeck, Massachusetts Institute of Technology; Bruce D. Walker, Massachusetts Institute of Technology; Laura M. Walker, Scripps Research Institute; Andrew B. Ward, Scripps Research Institute; Ian A. Wilson, Scripps Research Institute; Richard Wyatt, Scripps Research Institute
• Language: English
• Date: 2012-10-18
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Inc.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.chom.2012.09.008
• Title of Journal or Parent Work: Cell Host and Microbe
• ISSN: 1931-3128
• Volume: 12
• Issue: 4
• Start Page: 396
• End Page: 407
• Keywords: B-CELLS; RESPIRATORY SYNCYTIAL VIRUS; T FOLLICULAR HELPER; SITE-SPECIFIC ANALYSIS; Microbiology; CD4 BINDING-SITE; VESICULAR STOMATITIS-VIRUS; Life Sciences & Biomedicine; ENVELOPE GLYCOPROTEINS; Virology; Parasitology; Science & Technology; AUTOLOGOUS NEUTRALIZING ANTIBODY; IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES
• Research Categories: Health Sciences, Immunology

Abstract

Despite numerous attempts over many years to develop an HIV vaccine based on classical strategies, none has convincingly succeeded to date. A number of approaches are being pursued in the field, including building upon possible efficacy indicated by the recent RV144 clinical trial, which combined two HIV vaccines. Here, we argue for an approach based, in part, on understanding the HIV envelope spike and its interaction with broadly neutralizing antibodies (bnAbs) at the molecular level and using this understanding to design immunogens as possible vaccines. BnAbs can protect against virus challenge in animal models, and many such antibodies have been isolated recently. We further propose that studies focused on how best to provide T cell help to B cells that produce bnAbs are crucial for optimal immunization strategies. The synthesis of rational immunogen design and immunization strategies, together with iterative improvements, offers great promise for advancing toward an HIV vaccine.