title: Analysis of immunoglobulin transcripts and hypermutation following SHIV(AD8) infection and protein-plus-adjuvant immunization.
abstract: Developing predictive animal models to assess how candidate vaccines and infection influence the ontogenies of Envelope (Env)-specific antibodies is critical for the development of an HIV vaccine. Here we use two nonhuman primate models to compare the roles of antigen persistence, diversity and innate immunity. We perform longitudinal analyses of HIV Env-specific B-cell receptor responses to SHIV(AD8) infection and Env protein vaccination with eight different adjuvants. A subset of the SHIV(AD8)-infected animals with higher viral loads and greater Env diversity show increased neutralization associated with increasing somatic hypermutation (SHM) levels over time. The use of adjuvants results in increased ELISA titres but does not affect the mean SHM levels or CDR H3 lengths. Our study shows how the ontogeny of Env-specific B cells can be tracked, and provides insights into the requirements for developing neutralizing antibodies that should facilitate translation to human vaccine studies.
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Joseph R
authors: JR
authors: Francica
authors: Department of Biochemistry, Columbia University, New York, New York 10032, USA.
authors: Zizhang
authors: Z
authors: Sheng
authors: 1] Department of Biochemistry, Columbia University, New York, New York 10032, USA [2] State Key Laboratory of Organ Failure Research and National Clinical Research Center for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors: Zhenhai
authors: Z
authors: Zhang
authors: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Yoshiaki
authors: Y
authors: Nishimura
authors: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Masashi
authors: M
authors: Shingai
authors: Department of Microbiology and Immunology, Boston University, Boston, Massachusetts 02118, USA.
authors: Akshaya
authors: A
authors: Ramesh
authors: AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory, Frederick, Maryland 21702, USA.
authors: Brandon F
authors: BF
authors: Keele
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Stephen D
authors: SD
authors: Schmidt
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Barbara J
authors: BJ
authors: Flynn
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Sam
authors: S
authors: Darko
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Rebecca M
authors: RM
authors: Lynch
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Takuya
authors: T
authors: Yamamoto
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Rodrigo
authors: R
authors: Matus-Nicodemos
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: David
authors: D
authors: Wolinsky
authors: Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Martha
authors: M
authors: Nason
authors: Novartis Vaccines and Diagnostics, Cambridge, Massachusetts 02139, USA.
authors: Nicholas M
authors: NM
authors: Valiante
authors: Novartis Vaccines and Diagnostics, Cambridge, Massachusetts 02139, USA.
authors: Padma
authors: P
authors: Malyala
authors: Novartis Vaccines and Diagnostics, Cambridge, Massachusetts 02139, USA.
authors: Ennio
authors: E
authors: De Gregorio
authors: Novartis Vaccines and Diagnostics, Cambridge, Massachusetts 02139, USA.
authors: Susan W
authors: SW
authors: Barnett
authors: Novartis Vaccines and Diagnostics, Cambridge, Massachusetts 02139, USA.
authors: Manmohan
authors: M
authors: Singh
authors: Novartis Vaccines and Diagnostics, Cambridge, Massachusetts 02139, USA.
authors: Derek T
authors: DT
authors: O'Hagan
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Richard A
authors: RA
authors: Koup
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: John R
authors: JR
authors: Mascola
authors: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Malcolm A
authors: MA
authors: Martin
authors: Department of Microbiology and Immunology, Boston University, Boston, Massachusetts 02118, USA.
authors: Thomas B
authors: TB
authors: Kepler
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Daniel C
authors: DC
authors: Douek
authors: Department of Biochemistry, Columbia University, New York, New York 10032, USA.
authors: Lawrence
authors: L
authors: Shapiro
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Robert A
authors: RA
authors: Seder
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology*; D016180:Lentivirus Infections / Q000276:immunology / Q000517:prevention & control; D017958:Lentiviruses, Primate / Q000276:immunology; D008137:Longitudinal Studies; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000032:analysis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D019562:Viral Load; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D007136:Immunoglobulins; D012333:RNA, Messenger; D012367:RNA, Viral; D054299:env Gene Products, Human Immunodeficiency Virus