title: Diverse antibody genetic and recognition properties revealed following HIV-1 envelope glycoprotein immunization.
abstract: Isolation of mAbs elicited by vaccination provides opportunities to define the development of effective immunity. Ab responses elicited by current HIV-1 envelope glycoprotein (Env) immunogens display narrow neutralizing activity with limited capacity to block infection by tier 2 viruses. Intense work in the field suggests that improved Env immunogens are forthcoming, and it is therefore important to concurrently develop approaches to investigate the quality of vaccine-elicited responses at a higher level of resolution. In this study, we cloned a representative set of mAbs elicited by a model Env immunogen in rhesus macaques and comprehensively characterized their genetic and functional properties. The mAbs were genetically diverse, even within groups of Abs targeting the same subregion of Env, consistent with a highly polyclonal response. mAbs directed against two subdeterminants of Env, the CD4 binding site and V region 3, could in part account for the neutralizing activity observed in the plasma of the animal from which they were cloned, demonstrating the power of mAb isolation for a detailed understanding of the elicited response. Finally, through comparative analyses of mAb binding and neutralizing capacity of HIV-1 using matched Envs, we demonstrate complex relationships between epitope recognition and accessibility, highlighting the protective quaternary packing of the HIV-1 spike relative to vaccine-induced mAbs.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden;
authors.forename: Ganesh E
authors.initials: GE
authors.lastname: Phad
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden;
authors.forename: Néstor
authors.initials: N
authors.lastname: Vázquez Bernat
authors.affiliation: International AIDS Vaccine Initiative, Neutralizing Antibody Center, Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037;
authors.forename: Yu
authors.initials: Y
authors.lastname: Feng
authors.affiliation: International AIDS Vaccine Initiative, Neutralizing Antibody Center, Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037;
authors.forename: Jidnyasa
authors.initials: J
authors.lastname: Ingale
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden;
authors.forename: Paola Andrea
authors.initials: PA
authors.lastname: Martinez Murillo
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Sijy
authors.initials: S
authors.lastname: O'Dell
authors.affiliation: International AIDS Vaccine Initiative, Neutralizing Antibody Center, Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850; and.
authors.forename: Yuxing
authors.initials: Y
authors.lastname: Li
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892;
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; Immunology Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Sundling
authors.affiliation: International AIDS Vaccine Initiative, Neutralizing Antibody Center, Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037;
authors.forename: Richard T
authors.initials: RT
authors.lastname: Wyatt
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden; Gunilla.Karlsson.Hedestam@ki.se.
authors.forename: Gunilla B
authors.initials: GB
authors.lastname: Karlsson Hedestam
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing; D000916:Antibody Diversity / Q000235:genetics* / Q000276:immunology*; D001666:Binding Sites, Antibody / Q000235:genetics; D015704:CD4 Antigens / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics; D015497:HIV-1 / Q000276:immunology*; D007114:Immunization; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D011994:Recombinant Proteins; D054299:env Gene Products, Human Immunodeficiency Virus