RAIN: machine learning-based identification for HIV-1 bNAbs.

Journal: Nature communications
PMID: 38914562

Abstract

Broadly neutralizing antibodies (bNAbs) are promising candidates for the treatment and prevention of HIV-1 infections. Despite their critical importance, automatic detection of HIV-1 bNAbs from immune repertoires is still lacking. Here, we develop a straightforward computational method for the Rapid Automatic Identification of bNAbs (RAIN) based on machine learning methods. In contrast to other approaches, which use one-hot encoding amino acid sequences or structural alignment for prediction, RAIN uses a combination of selected sequence-based features for the accurate prediction of HIV-1 bNAbs. We demonstrate the performance of our approach on non-biased, experimentally obtained and sequenced BCR repertoires from HIV-1 immune donors. RAIN processing leads to the successful identification of distinct HIV-1 bNAbs targeting the CD4-binding site of the envelope glycoprotein. In addition, we validate the identified bNAbs using an in vitro neutralization assay and we solve the structure of one of them in complex with the soluble native-like heterotrimeric envelope glycoprotein by single-particle cryo-electron microscopy (cryo-EM). Overall, we propose a method to facilitate and accelerate HIV-1 bNAbs discovery from non-selected immune repertoires.

Authors

  • Mathilde Foglierini
    Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
  • Pauline Nortier
    Department of Medicine, Service of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Rachel Schelling
    Department of Medicine, Service of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Rahel R Winiger
    Department of Medicine, Service of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Philippe Jacquet
    Scientific Computing and Research Support Unit, University of Lausanne, Lausanne, Switzerland.
  • Sijy O'Dell
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Davide Demurtas
    Interdisciplinary center of electron microscopy, CIME, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Maxmillian Mpina
    Ifakara Health Institute, Bagamoyo, United Republic of Tanzania.
  • Omar Lweno
    Ifakara Health Institute, Bagamoyo, United Republic of Tanzania.
  • Yannick D Muller
    Department of Medicine, Service of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Constantinos Petrovas
    Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland.
  • Claudia Daubenberger
    Department of Medical Parasitology and Infection Biology, Clinical Immunology Unit, Swiss Tropical and Public Health Institute, Basel, Switzerland.
  • Matthieu Perreau
    Department of Medicine, Service of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Nicole A Doria-Rose
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, MD, USA.
  • Raphael Gottardo
    Molecular Biology and Biochemistry Department, Simon Fraser University, Burnaby, BC V5A 1S6, Canada, Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, Canada, Department of Neurology, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY 14203, USA, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA, Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, MD 20892, USA, School of Dental Medicine, University at Buffalo, NY 14214-8006, USA, J. Craig Venter Institute, La Jolla, CA 92037, USA, Department of Pathology, University of California, San Diego, CA 92093, USA.
  • Laurent Perez
    Department of Medicine, Service of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. laurent.perez@chuv.ch.

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