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Particulate Array of Well-Ordered HIV Clade C Env Trimers Elicits Neutralizing Antibodies that Display a Unique V2 Cap Approach.
Martinez-Murillo, Paola; Tran, Karen; Guenaga, Javier; Lindgren, Gustaf; Àdori, Monika; Feng, Yu; Phad, Ganesh E; Vázquez Bernat, Néstor; Bale, Shridhar; Ingale, Jidnyasa; Dubrovskaya, Viktoriya; O'Dell, Sijy; Pramanik, Lotta; Spångberg, Mats; Corcoran, Martin; Loré, Karin; Mascola, John R; Wyatt, Richard T; Karlsson Hedestam, Gunilla B.
Affiliation
  • Martinez-Murillo P; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
  • Tran K; IAVI Neutralizing Antibody Center, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Guenaga J; IAVI Neutralizing Antibody Center, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Lindgren G; Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, 171 77 Solna, Sweden.
  • Àdori M; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
  • Feng Y; IAVI Neutralizing Antibody Center, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Phad GE; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
  • Vázquez Bernat N; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
  • Bale S; IAVI Neutralizing Antibody Center, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Ingale J; IAVI Neutralizing Antibody Center, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Dubrovskaya V; IAVI Neutralizing Antibody Center, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • O'Dell S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Pramanik L; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
  • Spångberg M; Astrid Fagraeus Laboratory, Comparative Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
  • Corcoran M; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
  • Loré K; Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, 171 77 Solna, Sweden.
  • Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Wyatt RT; IAVI Neutralizing Antibody Center, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: wyatt@scripps.edu.
  • Karlsson Hedestam GB; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Electronic address: gunilla.karlsson.hedestam@ki.se.
Immunity ; 46(5): 804-817.e7, 2017 05 16.
Article in En | MEDLINE | ID: mdl-28514687
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.
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Full text: 1 Collection: 01-internacional Health context: 2_ODS3 Database: MEDLINE Main subject: Peptide Fragments / HIV Antibodies / HIV-1 / Env Gene Products, Human Immunodeficiency Virus / Protein Multimerization / Antibodies, Neutralizing Limits: Humans Language: En Journal: Immunity Year: 2017 Document type: Article
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Full text: 1 Collection: 01-internacional Health context: 2_ODS3 Database: MEDLINE Main subject: Peptide Fragments / HIV Antibodies / HIV-1 / Env Gene Products, Human Immunodeficiency Virus / Protein Multimerization / Antibodies, Neutralizing Limits: Humans Language: En Journal: Immunity Year: 2017 Document type: Article