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Your search keyword '"Àdori M"' showing total 2 results
Start Over Author "Àdori M" Topic env gene products, human immunodeficiency virus
2 results on '"Àdori M"'

1. Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses.

Author

Phad GE, Pushparaj P, Tran K, Dubrovskaya V, Àdori M, Martinez-Murillo P, Vázquez Bernat N, Singh S, Dionne G, O'Dell S, Bhullar K, Narang S, Sorini C, Villablanca EJ, Sundling C, Murrell B, Mascola JR, Shapiro L, Pancera M, Martin M, Corcoran M, Wyatt RT, and Karlsson Hedestam GB

Subjects
Animals, Antibodies, Neutralizing immunology, Cell Lineage genetics, Cell Lineage immunology, Cells, Cultured, Complementarity Determining Regions genetics, Female, HIV Antibodies immunology, HIV Infections virology, HIV-1 chemistry, High-Throughput Nucleotide Sequencing, Immunoglobulin Heavy Chains genetics, Macaca mulatta, Reverse Transcriptase Polymerase Chain Reaction, Single-Cell Analysis, Somatic Hypermutation, Immunoglobulin, AIDS Vaccines immunology, B-Lymphocytes immunology, HIV Infections immunology, HIV Infections prevention & control, HIV-1 immunology, Vaccination, env Gene Products, Human Immunodeficiency Virus immunology
Abstract

Well-ordered HIV-1 envelope glycoprotein (Env) trimers are prioritized for clinical evaluation, and there is a need for an improved understanding about how elicited B cell responses evolve following immunization. To accomplish this, we prime-boosted rhesus macaques with clade C NFL trimers and identified 180 unique Ab lineages from ∼1,000 single-sorted Env-specific memory B cells. We traced all lineages in high-throughput heavy chain (HC) repertoire (Rep-seq) data generated from multiple immune compartments and time points and expressed several as monoclonal Abs (mAbs). Our results revealed broad dissemination and high levels of somatic hypermutation (SHM) of most lineages, including tier 2 virus neutralizing lineages, following boosting. SHM was highest in the Ab complementarity determining regions (CDRs) but also surprisingly high in the framework regions (FRs), especially FR3. Our results demonstrate the capacity of the immune system to affinity-mature large numbers of Env-specific B cell lineages simultaneously, supporting the use of regimens consisting of repeated boosts to improve each Ab, even those belonging to less expanded lineages., (© 2019 Phad et al.)

Published
2020
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2. Particulate Array of Well-Ordered HIV Clade C Env Trimers Elicits Neutralizing Antibodies that Display a Unique V2 Cap Approach.

Author

Martinez-Murillo P, Tran K, Guenaga J, Lindgren G, Àdori M, Feng Y, Phad GE, Vázquez Bernat N, Bale S, Ingale J, Dubrovskaya V, O'Dell S, Pramanik L, Spångberg M, Corcoran M, Loré K, Mascola JR, Wyatt RT, and Karlsson Hedestam GB

Subjects
Antibodies, Neutralizing chemistry, Antibodies, Neutralizing metabolism, Epitope Mapping, Epitopes chemistry, Epitopes immunology, HIV Antibodies chemistry, HIV Antibodies metabolism, HIV-1 classification, HIV-1 genetics, Humans, Immunization, Models, Molecular, Molecular Docking Simulation, Peptide Fragments chemistry, Peptide Fragments metabolism, Protein Binding, Protein Conformation, Virion chemistry, Virion immunology, Virion ultrastructure, env Gene Products, Human Immunodeficiency Virus genetics, Antibodies, Neutralizing immunology, HIV Antibodies immunology, HIV-1 immunology, Peptide Fragments immunology, Protein Multimerization immunology, env Gene Products, Human Immunodeficiency Virus chemistry, env Gene Products, Human Immunodeficiency Virus immunology
Abstract

The development of soluble envelope glycoprotein (Env) mimetics displaying ordered trimeric symmetry has ushered in a new era in HIV-1 vaccination. The recently reported native, flexibly linked (NFL) design allows the generation of native-like trimers from clinical isolates at high yields and homogeneity. As the majority of infections world-wide are of the clade C subtype, we examined responses in non-human primates to well-ordered subtype C 16055 trimers administered in soluble or high-density liposomal formats. We detected superior germinal center formation and enhanced autologous neutralizing antibodies against the neutralization-resistant (tier 2) 16055 virus following inoculation of liposome-arrayed trimers. Epitope mapping of the neutralizing monoclonal antibodies (mAbs) indicated major contacts with the V2 apex, and 3D electron microscopy reconstructions of Fab-trimer complexes revealed a horizontal binding angle to the Env spike. These vaccine-elicited mAbs target the V2 cap, demonstrating a means to accomplish tier 2 virus neutralization by penetrating the dense N-glycan shield., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Published
2017
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