title: Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability.
abstract: The simian immunodeficiency virus (SIV) challenge model of lentiviral infection is often used as a model to human immunodeficiency virus type 1 (HIV-1) for studying vaccine mediated and immune correlates of protection. However, knowledge of the structure of the SIV envelope (Env) glycoprotein is limited, as is knowledge of binding specificity, function and potential efficacy of SIV antibody responses. In this study we describe the use of a competitive probe binding sort strategy as well as scaffolded probes for targeted isolation of SIV Env-specific monoclonal antibodies (mAbs). We isolated nearly 70 SIV-specific mAbs directed against major sites of SIV Env vulnerability analogous to broadly neutralizing antibody (bnAb) targets of HIV-1, namely, the CD4 binding site (CD4bs), CD4-induced (CD4i)-site, peptide epitopes in variable loops 1, 2 and 3 (V1, V2, V3) and potentially glycan targets of SIV Env. The range of SIV mAbs isolated includes those exhibiting varying degrees of neutralization breadth and potency as well as others that demonstrated binding but not neutralization. Several SIV mAbs displayed broad and potent neutralization of a diverse panel of 20 SIV viral isolates with some also neutralizing HIV-2(7312A). This extensive panel of SIV mAbs will facilitate more effective use of the SIV non-human primate (NHP) model for understanding the variables in development of a HIV vaccine or immunotherapy.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Rosemarie D
authors.initials: RD
authors.lastname: Mason
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Hugh C
authors.initials: HC
authors.lastname: Welles
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Cameron
authors.initials: C
authors.lastname: Adams
authors.affiliation: International AIDS Vaccine Initiative (IAVI) HIV Vaccine Design Program, Translational Health Science and Technology Institute, Haryana, India.
authors.forename: Bimal K
authors.initials: BK
authors.lastname: Chakrabarti
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Jason
authors.initials: J
authors.lastname: Gorman
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Tongqing
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Nguyen
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Sijy
authors.initials: S
authors.lastname: O'Dell
authors.affiliation: Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Lusvarghi
authors.affiliation: Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Carole A
authors.initials: CA
authors.lastname: Bewley
authors.affiliation: Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.affiliation: Department of Biochemistry and Molecular Biophysics and Department of Systems Biology, Columbia University, New York, New York, United States of America.
authors.forename: Zizhang
authors.initials: Z
authors.lastname: Sheng
authors.affiliation: Department of Biochemistry and Molecular Biophysics and Department of Systems Biology, Columbia University, New York, New York, United States of America.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Shapiro
authors.affiliation: IAVI Neutralizing Antibody Center, Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Wyatt
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kwong
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States of America.
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D001665:Binding Sites; D000939:Epitopes / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D009500:Neutralization Tests / Q000379:methods; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D015686:Gene Products, env; D015483:HIV Antibodies