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Super Potent Bispecific Llama VHH Antibodies Neutralize HIV via a Combination of gp41 and gp120 Epitopes.
Strokappe, Nika M; Hock, Miriam; Rutten, Lucy; Mccoy, Laura E; Back, Jaap W; Caillat, Christophe; Haffke, Matthias; Weiss, Robin A; Weissenhorn, Winfried; Verrips, Theo.
Afiliación
  • Strokappe NM; Department of Biology, Faculty of Sciences, Utrecht University, 3584 CH Utrecht, The Netherlands. n.m.strokappe@gmail.com.
  • Hock M; QVQ Holding bv, Yalelaan 1, 3584 CL Utrecht, The Netherlands. n.m.strokappe@gmail.com.
  • Rutten L; Institute de Biologie Structurale (IBS), CNRS, CEA, Université Grenoble Alpes, F-38000 Grenoble, France. Miriam.hock@googlemail.com.
  • Mccoy LE; Immunocore Ltd., 101 Park Drive, Milto, Abingdon OX14 4RY, UK. Miriam.hock@googlemail.com.
  • Back JW; Department of Biology, Faculty of Sciences, Utrecht University, 3584 CH Utrecht, The Netherlands. lucy.rutten@gmail.com.
  • Caillat C; QVQ Holding bv, Yalelaan 1, 3584 CL Utrecht, The Netherlands. lucy.rutten@gmail.com.
  • Haffke M; Division of Infection and Immunity, University College London, London WC1E 6BT, UK. l.mccoy@ucl.ac.uk.
  • Weiss RA; Pepscan B.V., Zuidersluisweg 2, 8243 RC Lelystad, The Netherlands. jjaapwillemback@eurofins.com.
  • Weissenhorn W; Institute de Biologie Structurale (IBS), CNRS, CEA, Université Grenoble Alpes, F-38000 Grenoble, France. christophe.caillat@ibs.fr.
  • Verrips T; European Molecular Biology Laboratory, Grenoble Outstation, 6 rue Jules Horowitz, 38042 Grenoble, France. Matthias.haffke@novartis.com.
Antibodies (Basel) ; 8(2)2019 Jun 18.
Article en En | MEDLINE | ID: mdl-31544844
Broad and potent neutralizing llama single domain antibodies (VHH) against HIV-1 targeting the CD4 binding site (CD4bs) have previously been isolated upon llama immunization. Here we describe the epitopes of three additional VHH groups selected from phage libraries. The 2E7 group binds to a new linear epitope in the first heptad repeat of gp41 that is only exposed in the fusion-intermediate conformation. The 1B5 group competes with co-receptor binding and the 1F10 group interacts with the crown of the gp120 V3 loop, occluded in native Env. We present biophysical and structural details on the 2E7 interaction with gp41. In order to further increase breadth and potency, we constructed bi-specific VHH. The combination of CD4bs VHH (J3/3E3) with 2E7 group VHH enhanced strain-specific neutralization with potencies up to 1400-fold higher than the mixture of the individual VHHs. Thus, these new bivalent VHH are potent new tools to develop therapeutic approaches or microbicide intervention.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Antibodies (Basel) Año: 2019 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Antibodies (Basel) Año: 2019 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Suiza