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A Computationally Designed Hemagglutinin Stem-Binding Protein Provides In Vivo Protection from Influenza Independent of a Host Immune Response

Academic Article
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Overview

related to degree

  • Lee, Peter S., Ph.D. in Biology, Scripps Research 2009 - 2014

authors

  • Koday, M. T.
  • Nelson, J.
  • Chevalier, A.
  • Koday, M.
  • Kalinoski, H.
  • Stewart, L.
  • Carter, L.
  • Nieusma, T.
  • Lee, Peter S.
  • Ward, Andrew
  • Wilson, Ian
  • Dagley, A.
  • Smee, D. F.
  • Baker, D.
  • Fuller, D. H.

publication date

  • February 2016

journal

  • PLoS Pathogens  Journal

abstract

  • Broadly neutralizing antibodies targeting a highly conserved region in the hemagglutinin (HA) stem protect against influenza infection. Here, we investigate the protective efficacy of a protein (HB36.6) computationally designed to bind with high affinity to the same region in the HA stem. We show that intranasal delivery of HB36.6 affords protection in mice lethally challenged with diverse strains of influenza independent of Fc-mediated effector functions or a host antiviral immune response. This designed protein prevents infection when given as a single dose of 6.0 mg/kg up to 48 hours before viral challenge and significantly reduces disease when administered as a daily therapeutic after challenge. A single dose of 10.0 mg/kg HB36.6 administered 1-day post-challenge resulted in substantially better protection than 10 doses of oseltamivir administered twice daily for 5 days. Thus, binding of HB36.6 to the influenza HA stem region alone, independent of a host response, is sufficient to reduce viral infection and replication in vivo. These studies demonstrate the potential of computationally designed binding proteins as a new class of antivirals for influenza.

subject areas

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Carrier Proteins
  • Cytokines
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Humans
  • Influenza A virus
  • Influenza, Human
  • Mice
  • Models, Molecular
  • Mutation
  • Virus Replication
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Identity

PubMed Central ID

  • PMC4742065

International Standard Serial Number (ISSN)

  • 1553-7366

Digital Object Identifier (DOI)

  • 10.1371/journal.ppat.1005409

PubMed ID

  • 26845438
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Additional Document Info

volume

  • 12

issue

  • 2

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