title: Characterization of human IgG repertoires in an acute HIV-1 infection.
abstract: All known broadly neutralizing antibodies (bnAbs) are highly somatically mutated and therefore significantly differ from their germline predecessors. Thus although the mature bnAbs bind to conserved epitopes of the HIV-1 envelope glycoprotein (Env) with high affinity their germline predecessors do not or weakly bind Envs failing to initiate an effective immune response. The identification of less somatically mutated bnAbs and/or antibody maturation intermediates that are clonally related to bnAbs may be useful to circumvent the major problem of initiating immune responses leading to elicitation of bnAbs. Here, we describe the identification of IgG antibodies from an acutely HIV-1-infected patient using a combination of phage display and high-throughput sequencing. We found two antibodies with only a single point mutation in the V region of their heavy chain variable domains compared to their putative germline predecessors which bound with high affinity to several Envs. They targeted the Env gp41 and did not neutralize HIV-1. Using high-throughput sequencing, we identified several highly abundant CDR3s, germline-like as well as somatically mutated V genes in the VH/VL repertoires of the patient which may provide antibody intermediates corresponding to known bnAbs as templates for design of novel HIV-1 vaccine immunogens.
authors.affiliation: Protein Interactions Group, National Cancer Institute, National Institutes of Health (NIH), Frederick, Maryland 21702, USA. chenw3@mail.nih.gov
authors.forename: Weizao
authors.initials: W
authors.lastname: Chen
authors.forename: Ponraj
authors.initials: P
authors.lastname: Prabakaran
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Yang
authors.initials: Y
authors.lastname: Feng
authors.forename: Emily D
authors.initials: ED
authors.lastname: Streaker
authors.forename: Dimiter S
authors.initials: DS
authors.lastname: Dimitrov
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D061505:Cell Surface Display Techniques / Q000379:methods; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology*; D008969:Molecular Sequence Data; D009154:Mutation; D017423:Sequence Analysis, RNA
chemical_list: D057134:Antibodies, Neutralizing; D001323:Autoantibodies; D007074:Immunoglobulin G