title: Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology.
abstract: While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As antibodies mediate an array of extra-neutralizing Fc functions, when neutralization fails to predict protection, investigating Fc-mediated activity may help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine trials. Each vaccine regimen induced a unique humoral "Fc fingerprint." Moreover, analysis of case:control data from the first moderately protective HIV vaccine trial, RV144, pointed to mechanistic insights into immune complex composition that may underlie protective immunity to HIV. Thus, multi-dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines against pathogens for which correlates of protection remain elusive.
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Amy W
authors.initials: AW
authors.lastname: Chung
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Manu P
authors.initials: MP
authors.lastname: Kumar
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Kelly B
authors.initials: KB
authors.lastname: Arnold
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Wen Han
authors.initials: WH
authors.lastname: Yu
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Schoen
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Dunphy
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Suscovich
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
authors.forename: Caitlyn
authors.initials: C
authors.lastname: Linde
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
authors.forename: Alison E
authors.initials: AE
authors.lastname: Mahan
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Hoffner
authors.affiliation: Department of Molecular Virology and Pathogenesis, Walter Reed Army Institute of Research, U.S. Military HIV Research Program, Silver Spring, MD 20910, USA; Institute for Medical Biology, University Hospital Essen, University Duisburg-Essen, Essen 45141, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Streeck
authors.affiliation: Thayer School of Engineering at Dartmouth, Hanover, NH 03755, USA.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Ackerman
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.affiliation: Crucell Holland B.V., The Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden 2333, the Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.affiliation: Crucell Holland B.V., The Janssen Pharmaceutical Companies of Johnson & Johnson, Leiden 2333, the Netherlands.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Pau
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02215, USA.
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.affiliation: Department of Molecular Virology and Pathogenesis, Walter Reed Army Institute of Research, U.S. Military HIV Research Program, Silver Spring, MD 20910, USA; International Vaccine Institute, Seoul 151-742, Republic of Korea.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Molecular Virology and Pathogenesis, Walter Reed Army Institute of Research, U.S. Military HIV Research Program, Silver Spring, MD 20910, USA.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: lauffen@mit.edu.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Lauffenburger
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Electronic address: galter@mgh.harvard.edu.
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D000936:Antigen-Antibody Complex / Q000276:immunology; D002986:Clinical Trials as Topic; D015195:Drug Design; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D011961:Receptors, Fc