title: Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies.
abstract: Development of strategies for induction of HIV-1 broadly neutralizing antibodies (bnAbs) by vaccines is a priority. Determining the steps of bnAb induction in HIV-1-infected individuals who make bnAbs is a key strategy for immunogen design. Here, we study the B cell response in a bnAb-producing individual and report cooperation between two B cell lineages to drive bnAb development. We isolated a virus-neutralizing antibody lineage that targeted an envelope region (loop D) and selected virus escape mutants that resulted in both enhanced bnAb lineage envelope binding and escape mutant neutralization-traits associated with increased B cell antigen drive. Thus, in this individual, two B cell lineages cooperated to induce the development of bnAbs. Design of vaccine immunogens that simultaneously drive both helper and broadly neutralizing B cell lineages may be important for vaccine-induced recapitulation of events that transpire during the maturation of neutralizing antibodies in HIV-1-infected individuals.
authors: Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA. Electronic address: fgao@duke.edu.
authors: Feng
authors: F
authors: Gao
authors: Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA.
authors: Mattia
authors: M
authors: Bonsignori
authors: Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA.
authors: Hua-Xin
authors: HX
authors: Liao
authors: Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA.
authors: Amit
authors: A
authors: Kumar
authors: Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA.
authors: Shi-Mao
authors: SM
authors: Xia
authors: Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA.
authors: Xiaozhi
authors: X
authors: Lu
authors: Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA.
authors: Fangping
authors: F
authors: Cai
authors: Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA.
authors: Kwan-Ki
authors: KK
authors: Hwang
authors: Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA.
authors: Hongshuo
authors: H
authors: Song
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Tongqing
authors: T
authors: Zhou
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Rebecca M
authors: RM
authors: Lynch
authors: Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA.
authors: S Munir
authors: SM
authors: Alam
authors: Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA.
authors: M Anthony
authors: MA
authors: Moody
authors: Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA.
authors: Guido
authors: G
authors: Ferrari
authors: Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA.
authors: Mark
authors: M
authors: Berrong
authors: Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA.
authors: Garnett
authors: G
authors: Kelsoe
authors: Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: George M
authors: GM
authors: Shaw
authors: Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Beatrice H
authors: BH
authors: Hahn
authors: Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA.
authors: David C
authors: DC
authors: Montefiori
authors: UNC Project, Lilongwe, Malawi; Departments of Health Policy and Management, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors: Gift
authors: G
authors: Kamanga
authors: Departments of Medicine, Epidemiology and Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors: Myron S
authors: MS
authors: Cohen
authors: Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87544, USA.
authors: Peter
authors: P
authors: Hraber
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Peter D
authors: PD
authors: Kwong
authors: Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87544, USA.
authors: Bette T
authors: BT
authors: Korber
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: John R
authors: JR
authors: Mascola
authors: Department of Microbiology, Boston University, Boston, MA 02215, USA.
authors: Thomas B
authors: TB
authors: Kepler
authors: Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, Durham NC 27710, USA; The Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham NC 27710, USA. Electronic address: barton.haynes@duke.edu.
authors: Barton F
authors: BF
authors: Haynes
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry* / Q000276:immunology*; D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D057131:Immune Evasion; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus