0
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Anti-hemagglutinin monomeric nanobody provides prophylactic immunity against H1 subtype influenza A viruses

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Influenza viruses constitute a major threat to human health globally. The viral surface glycoprotein hemagglutinin (HA) is the immunodominant antigen, contains the site for binding to the cellular receptor (RBS), and it is the major target of neutralizing antibody responses post-infection. We developed llama-derived single chain antibody fragments (VHHs) specific for type A influenza virus. Four VHHs were identified and further characterized. VHH D81 bound residues in the proximity of the C-terminal region of HA1 of H1 and H5 subtypes, and showed weak neutralizing activity, whereas VHH B33 bound residues in the proximity of the N-terminal region of the HA’s stem domain (HA2) of H1, H5, and H9 subtypes, and showed no neutralizing activity. Of most relevance, VHHs E13 and G41 recognized highly conserved conformational epitopes on the H1 HA’s globular domain (HA1) and showed high virus neutralizing activity (ranging between 0.94 to 0.01μM), when tested against several human H1N1 isolates. Additionally, E13 displayed abrogated virus replication of a panel of H1N1 strains spanning over 80 years of antigenic drift and isolated from human, avian, and swine origin. Interestingly, E13 conferred protection in vivo at a dose as low as 0.05 mg/kg. Mice treated with E13 intranasally resulted in undetectable virus challenge loads in the lungs at day 4 post-challenge. The transfer of sterilizing pan-H1 immunity, by a dose in the range of micrograms given intranasally, is of major significance for a monomeric VHH and supports the further development of E13 as an immunotherapeutic agent for the mitigation of influenza infections.

          Related collections

          Most cited references41

          • Record: found
          • Abstract: found
          • Article: not found

          UCSF Chimera--a visualization system for exploratory research and analysis.

          The design, implementation, and capabilities of an extensible visualization system, UCSF Chimera, are discussed. Chimera is segmented into a core that provides basic services and visualization, and extensions that provide most higher level functionality. This architecture ensures that the extension mechanism satisfies the demands of outside developers who wish to incorporate new features. Two unusual extensions are presented: Multiscale, which adds the ability to visualize large-scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales. Other extensions include Multalign Viewer, for showing multiple sequence alignments and associated structures; ViewDock, for screening docked ligand orientations; Movie, for replaying molecular dynamics trajectories; and Volume Viewer, for display and analysis of volumetric data. A discussion of the usage of Chimera in real-world situations is given, along with anticipated future directions. Chimera includes full user documentation, is free to academic and nonprofit users, and is available for Microsoft Windows, Linux, Apple Mac OS X, SGI IRIX, and HP Tru64 Unix from http://www.cgl.ucsf.edu/chimera/. Copyright 2004 Wiley Periodicals, Inc.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            SWISS-MODEL: homology modelling of protein structures and complexes

            Abstract Homology modelling has matured into an important technique in structural biology, significantly contributing to narrowing the gap between known protein sequences and experimentally determined structures. Fully automated workflows and servers simplify and streamline the homology modelling process, also allowing users without a specific computational expertise to generate reliable protein models and have easy access to modelling results, their visualization and interpretation. Here, we present an update to the SWISS-MODEL server, which pioneered the field of automated modelling 25 years ago and been continuously further developed. Recently, its functionality has been extended to the modelling of homo- and heteromeric complexes. Starting from the amino acid sequences of the interacting proteins, both the stoichiometry and the overall structure of the complex are inferred by homology modelling. Other major improvements include the implementation of a new modelling engine, ProMod3 and the introduction a new local model quality estimation method, QMEANDisCo. SWISS-MODEL is freely available at https://swissmodel.expasy.org.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The ClusPro web server for protein–protein docking

              ClusPro is a web server that performs rigid-body docking of two proteins by sampling billions of conformations. Low-energy docked structures are clustered, and centers of the largest clusters are used as likely models of the complex.
                Bookmark

                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Writing – original draft
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: Writing – original draft
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Investigation
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Methodology
                Role: MethodologyRole: Resources
                Role: Resources
                Role: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: ResourcesRole: Supervision
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLOS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                10 July 2024
                2024
                : 19
                : 7
                : e0301664
                Affiliations
                [1 ] Virology Institute IncuINTA (IVIT-CONICET), National Institute of Agricultural Technology, Hurlingham, Buenos Aires, Argentina
                [2 ] National Council for Scientific and Technical Research (CONICET), Buenos Aires City, Buenos Aires, Argentina
                [3 ] Institute of Science and Technology, Buenos Aires City, Buenos Aires, Argentina
                [4 ] Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America
                [5 ] National Institute of Infectious Diseases, Malbran Institute, Buenos Aires City, Buenos Aires, Argentina
                [6 ] Algenex S.L., Madrid, Spain
                Instituto Butantan, BRAZIL
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                [¤a]

                Current address: Center for the Study of Marine Systems, CESIMAR-CONICET, Puerto Madryn, Chubut, Argentina

                [¤b]

                Current address: Institute of Chemistry, Physics of Materials, Environment and Energy (INQUIMAE-CONICET), Faculty of Exact and Natural Sciences, University of Buenos Aires, Buenos Aires City, Buenos Aires, Argentina

                [¤c]

                Current address: Bahia Blanca Institute for Research in Biochemistry, University of the South, Bahía Blanca, Buenos Aires, Argentina

                Author information
                https://orcid.org/0000-0001-8508-6592
                https://orcid.org/0000-0003-2472-6028
                Article
                PONE-D-22-22678
                10.1371/journal.pone.0301664
                11236207
                38985719
                732db61d-c995-4171-902c-6a7f420f523c
                © 2024 Barbieri et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 12 August 2022
                : 20 March 2024
                Page count
                Figures: 6, Tables: 3, Pages: 24
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100010629, Fulbright Association;
                Award ID: Posdoctoral researcher. Cohort 2021. Completed
                Award Recipient :
                Funded by: ANPYCT
                Award ID: PICT 2014- 1437. Finalized.
                Award Recipient :
                Funded by: CONICET
                Award ID: Doctorade fellowship. 2019-2022. Finalized
                Award Recipient :
                This work was supported by PICT 2014-1437 from the Ministry of Science, technology and Innovation (MINCYT, https://www.argentina.gob.ar/ciencia/agencia) to VP, EB, LG and MP. EB, LII, VP, AW, MP are members of the Research Scientist Career at the National Research Council (CONICET, https://www.conicet.gov.ar/). CSH held a CONICET doctoral fellowship. MP held a Fulbright-CONICET research scholarship for the work performed at UGA, US. Algenex S.L. provided support in the form of salaries for JAME. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
                Categories
                Research Article
                Biology and life sciences
                Organisms
                Viruses
                RNA viruses
                Orthomyxoviruses
                Influenza viruses
                Influenza A virus
                H1N1
                Biology and life sciences
                Microbiology
                Medical microbiology
                Microbial pathogens
                Viral pathogens
                Orthomyxoviruses
                Influenza viruses
                Influenza A virus
                H1N1
                Medicine and health sciences
                Pathology and laboratory medicine
                Pathogens
                Microbial pathogens
                Viral pathogens
                Orthomyxoviruses
                Influenza viruses
                Influenza A virus
                H1N1
                Biology and life sciences
                Organisms
                Viruses
                Viral pathogens
                Orthomyxoviruses
                Influenza viruses
                Influenza A virus
                H1N1
                Biology and Life Sciences
                Physiology
                Immune Physiology
                Antibodies
                Biology and Life Sciences
                Immunology
                Immune System Proteins
                Antibodies
                Medicine and Health Sciences
                Immunology
                Immune System Proteins
                Antibodies
                Biology and Life Sciences
                Biochemistry
                Proteins
                Immune System Proteins
                Antibodies
                Research and Analysis Methods
                Immunologic Techniques
                Immunoassays
                Enzyme-Linked Immunoassays
                Medicine and Health Sciences
                Medical Conditions
                Infectious Diseases
                Viral Diseases
                Influenza
                Medicine and Health Sciences
                Public and Occupational Health
                Preventive Medicine
                Prophylaxis
                Physical Sciences
                Chemistry
                Polymer Chemistry
                Monomers
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Molecular Biology Assays and Analysis Techniques
                Molecular Biology Display Techniques
                Phage Display
                Research and Analysis Methods
                Molecular Biology Techniques
                Molecular Biology Assays and Analysis Techniques
                Molecular Biology Display Techniques
                Phage Display
                Biology and life sciences
                Organisms
                Viruses
                RNA viruses
                Orthomyxoviruses
                Influenza Viruses
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Viral Pathogens
                Orthomyxoviruses
                Influenza Viruses
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Viral Pathogens
                Orthomyxoviruses
                Influenza Viruses
                Biology and Life Sciences
                Organisms
                Viruses
                Viral Pathogens
                Orthomyxoviruses
                Influenza Viruses
                Custom metadata
                Additional data can be found in Supporting information 2 (URL: https://osf.io/kw5r9/), as well as in the Patent Application for Nanoantibodies (VHH) against the influenza virus H1N1 PUNTEL/ PARRENO - Record No. P220101478 - N.Ref. 31835. “NANOANTIBODIES (VHH) THAT BIND TO THE INFLUENZA VIRUS AND THEIR CORRESPONDING CDR3 DOMAINS, COMPOSITIONS, METHODS, USES AND KITS”.

                Uncategorized
                Uncategorized

                Comments

                Comment on this article