title: A Blueprint for HIV Vaccine Discovery.
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.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. burton@scripps.edu
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.forename: Salvatore T
authors.initials: ST
authors.lastname: Butera
authors.forename: Shane
authors.initials: S
authors.lastname: Crotty
authors.forename: Adam
authors.initials: A
authors.lastname: Godzik
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Kaufmann
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
authors.forename: Bali
authors.initials: B
authors.lastname: Pulendran
authors.forename: Chris N
authors.initials: CN
authors.lastname: Scanlan
authors.forename: William R
authors.initials: WR
authors.lastname: Schief
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.forename: Hendrik
authors.initials: H
authors.lastname: Streeck
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Laura M
authors.initials: LM
authors.lastname: Walker
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Ward
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
authors.forename: Richard
authors.initials: R
authors.lastname: Wyatt
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000486:Allergy and Immunology / Q000639:trends; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D015658:HIV Infections / Q000517:prevention & control; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral