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

Mendeley | Further Information

{"title"=>"A Computationally Designed Hemagglutinin Stem-Binding Protein Provides In Vivo Protection from Influenza Independent of a Host Immune Response", "type"=>"journal", "authors"=>[{"first_name"=>"Merika Treants", "last_name"=>"Koday", "scopus_author_id"=>"57151144800"}, {"first_name"=>"Jorgen", "last_name"=>"Nelson", "scopus_author_id"=>"56004470000"}, {"first_name"=>"Aaron", "last_name"=>"Chevalier", "scopus_author_id"=>"55246581500"}, {"first_name"=>"Michael", "last_name"=>"Koday", "scopus_author_id"=>"57151144700"}, {"first_name"=>"Hannah", "last_name"=>"Kalinoski", "scopus_author_id"=>"57151056400"}, {"first_name"=>"Lance", "last_name"=>"Stewart", "scopus_author_id"=>"35460249000"}, {"first_name"=>"Lauren", "last_name"=>"Carter", "scopus_author_id"=>"57150098700"}, {"first_name"=>"Travis", "last_name"=>"Nieusma", "scopus_author_id"=>"55487201500"}, {"first_name"=>"Peter S.", "last_name"=>"Lee", "scopus_author_id"=>"55246766200"}, {"first_name"=>"Andrew B.", "last_name"=>"Ward", "scopus_author_id"=>"55945233700"}, {"first_name"=>"Ian A.", "last_name"=>"Wilson", "scopus_author_id"=>"7401743864"}, {"first_name"=>"Ashley", "last_name"=>"Dagley", "scopus_author_id"=>"51863664600"}, {"first_name"=>"Donald F.", "last_name"=>"Smee", "scopus_author_id"=>"7007104795"}, {"first_name"=>"David", "last_name"=>"Baker", "scopus_author_id"=>"55463548900"}, {"first_name"=>"Deborah Heydenburg", "last_name"=>"Fuller", "scopus_author_id"=>"7102775401"}], "year"=>2016, "source"=>"PLoS Pathogens", "identifiers"=>{"sgr"=>"84959485747", "doi"=>"10.1371/journal.ppat.1005409", "pui"=>"608823277", "pmid"=>"26845438", "scopus"=>"2-s2.0-84959485747", "issn"=>"15537374", "isbn"=>"10.1371/journal.ppat.1005409"}, "id"=>"87a44987-c97f-3d9a-88d5-c62f3354d8a9", "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.", "link"=>"http://www.mendeley.com/research/computationally-designed-hemagglutinin-stembinding-protein-provides-vivo-protection-influenza-indepe", "reader_count"=>76, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>25, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>6, "Student > Master"=>9, "Other"=>4, "Student > Bachelor"=>10, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>25, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>6, "Student > Master"=>9, "Other"=>4, "Student > Bachelor"=>10, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>21, "Agricultural and Biological Sciences"=>22, "Medicine and Dentistry"=>6, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>12, "Computer Science"=>1, "Immunology and Microbiology"=>12}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Chemistry"=>{"Chemistry"=>12}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>12}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>22}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>21}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"South Korea"=>1, "Netherlands"=>1, "China"=>1, "United Kingdom"=>1, "South Africa"=>1}, "group_count"=>5}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84959485747"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84959485747?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84959485747&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84959485747&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84959485747", "dc:identifier"=>"SCOPUS_ID:84959485747", "eid"=>"2-s2.0-84959485747", "dc:title"=>"A Computationally Designed Hemagglutinin Stem-Binding Protein Provides In Vivo Protection from Influenza Independent of a Host Immune Response", "dc:creator"=>"Koday M.", "prism:publicationName"=>"PLoS Pathogens", "prism:issn"=>"15537366", "prism:eIssn"=>"15537374", "prism:volume"=>"12", "prism:issueIdentifier"=>"2", "prism:pageRange"=>nil, "prism:coverDate"=>"2016-02-01", "prism:coverDisplayDate"=>"February 2016", "prism:doi"=>"10.1371/journal.ppat.1005409", "citedby-count"=>"27", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"University of Washington, Seattle", "affiliation-city"=>"Seattle", "affiliation-country"=>"United States"}], "pubmed-id"=>"26845438", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e1005409", "source-id"=>"4000151809", "openaccess"=>"1", "openaccessFlag"=>true}

Article Coverage

Article Coverage Curated

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplospathogens%2Farticle%3Fid%3D10.1371%252Fjournal.ppat.1005409", "share_count"=>13, "like_count"=>276, "comment_count"=>49, "click_count"=>0, "total_count"=>338}

Twitter

Counter

  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"448", "xml_views"=>"3", "html_views"=>"3576"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"101", "xml_views"=>"1", "html_views"=>"569"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"77", "xml_views"=>"1", "html_views"=>"252"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"69", "xml_views"=>"0", "html_views"=>"234"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"44", "xml_views"=>"0", "html_views"=>"241"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"69", "xml_views"=>"0", "html_views"=>"201"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"52", "xml_views"=>"0", "html_views"=>"346"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"55", "xml_views"=>"0", "html_views"=>"244"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"47", "xml_views"=>"0", "html_views"=>"208"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"32", "xml_views"=>"0", "html_views"=>"244"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"48", "xml_views"=>"1", "html_views"=>"226"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"75", "xml_views"=>"2", "html_views"=>"330"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"41", "xml_views"=>"0", "html_views"=>"192"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"49", "xml_views"=>"0", "html_views"=>"272"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"29", "xml_views"=>"0", "html_views"=>"149"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"30", "xml_views"=>"2", "html_views"=>"181"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"21", "xml_views"=>"1", "html_views"=>"253"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"43", "xml_views"=>"0", "html_views"=>"153"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"201"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"298"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"30", "xml_views"=>"0", "html_views"=>"372"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"19", "xml_views"=>"1", "html_views"=>"328"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"26", "xml_views"=>"1", "html_views"=>"307"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"212"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"36", "xml_views"=>"0", "html_views"=>"65"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"77"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"15", "xml_views"=>"2", "html_views"=>"27"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"31", "xml_views"=>"0", "html_views"=>"46"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"21", "xml_views"=>"4", "html_views"=>"47"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"22", "xml_views"=>"4", "html_views"=>"31"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"26"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"13", "xml_views"=>"1", "html_views"=>"27"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"43", "xml_views"=>"1", "html_views"=>"38"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"23", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"45"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"40"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"20", "xml_views"=>"3", "html_views"=>"59"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"22", "xml_views"=>"1", "html_views"=>"39"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"11"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"33"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"26"}
  • {"month"=>"10", "year"=>"2019", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"58"}
  • {"month"=>"11", "year"=>"2019", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"12", "year"=>"2019", "pdf_views"=>"16", "xml_views"=>"1", "html_views"=>"21"}
  • {"month"=>"1", "year"=>"2020", "pdf_views"=>"25", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"2", "year"=>"2020", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"20"}
  • {"month"=>"3", "year"=>"2020", "pdf_views"=>"25", "xml_views"=>"1", "html_views"=>"32"}
  • {"month"=>"4", "year"=>"2020", "pdf_views"=>"44", "xml_views"=>"1", "html_views"=>"62"}
  • {"month"=>"5", "year"=>"2020", "pdf_views"=>"131", "xml_views"=>"1", "html_views"=>"48"}
  • {"month"=>"6", "year"=>"2020", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"30"}
  • {"month"=>"7", "year"=>"2020", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"8", "year"=>"2020", "pdf_views"=>"1", "xml_views"=>"3", "html_views"=>"14"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/4250959", "https://ndownloader.figshare.com/files/4250965", "https://ndownloader.figshare.com/files/4250968", "https://ndownloader.figshare.com/files/4250974"], "description"=>"<div><p>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 <i>in vivo</i>. These studies demonstrate the potential of computationally designed binding proteins as a new class of antivirals for influenza.</p></div>", "links"=>[], "tags"=>["influenza", "binding", "dose", "protein", "HA", "computationally", "host", "infection", "HB 36.6", "response", "mg", "region", "Host Immune Response", "protection", "challenge"], "article_id"=>2602075, "categories"=>["Biochemistry", "Medicine", "Microbiology", "Molecular Biology", "Pharmacology", "Immunology", "Biological Sciences not elsewhere classified", "Infectious Diseases", "Virology", "Computational Biology"], "users"=>["Merika Treants Koday", "Jorgen Nelson", "Aaron Chevalier", "Michael Koday", "Hannah Kalinoski", "Lance Stewart", "Lauren Carter", "Travis Nieusma", "Peter S. Lee", "Andrew B. Ward", "Ian A. Wilson", "Ashley Dagley", "Donald F. Smee", "David Baker", "Deborah Heydenburg Fuller"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005409.s001", "https://dx.doi.org/10.1371/journal.ppat.1005409.s002", "https://dx.doi.org/10.1371/journal.ppat.1005409.s003", "https://dx.doi.org/10.1371/journal.ppat.1005409.s004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Computationally_Designed_Hemagglutinin_Stem_Binding_Protein_Provides_In_Vivo_Protection_from_Influenza_Independent_of_a_Host_Immune_Response/2602075", "title"=>"A Computationally Designed Hemagglutinin Stem-Binding Protein Provides In Vivo Protection from Influenza Independent of a Host Immune Response", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2016-02-04 21:26:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/4251034"], "description"=>"<p>(a) Survival and weight change in BALB/c mice (n = 10 per group) that received 3.0 mg/kg of HB36.6 IN on day 0 (2 hours post-infection) or +1, +2, or +3 days post-infection (d.p.i.) or once daily on days +1–4 post-infection with 10 MLD<sub>50</sub> CA09 virus. As a control, the scaffold protein 1u84 (3.0 mg/kg) was IN administered once daily on days +1–4 post-infection. (b) Survival and weight change in BALB/c mice (n = 10 per group) that were challenged with 3 MLD<sub>50</sub> of CA09 virus and then received either a single dose of HB36.6 (0.1–10 mg/kg) IN on day +1 p.i., or oseltamivir (2.5 mg/kg/dose) by oral gavage twice a day on days +1–5 p.i. (10 doses total). Mean and SEM are shown. (c) Survival and weight change in BALB/c mice (n = 10 per group) that were challenged with 3 MLD<sub>50</sub> of CA09 virus and then received either a single dose of HB36.6 (1–10 mg/kg) IN on day +1 p.i., Oseltamivir (2.5 mg/kg/dose) by oral gavage twice a day on days +1–5 p.i. (10 doses total), or a combination of HB36.6 (1–10 mg/kg) by IN on day +1 plus oseltamivir (2.5 mg/kg/dose) by oral gavage twice a day on days +1–5 p.i. (10 doses total). Mean and SEM are shown.</p>", "links"=>[], "tags"=>["influenza", "binding", "dose", "protein", "HA", "computationally", "host", "infection", "HB 36.6", "response", "mg", "region", "Host Immune Response", "protection", "challenge"], "article_id"=>2602132, "categories"=>["Biochemistry", "Medicine", "Microbiology", "Molecular Biology", "Pharmacology", "Immunology", "Biological Sciences not elsewhere classified", "Infectious Diseases", "Virology", "Computational Biology"], "users"=>["Merika Treants Koday", "Jorgen Nelson", "Aaron Chevalier", "Michael Koday", "Hannah Kalinoski", "Lance Stewart", "Lauren Carter", "Travis Nieusma", "Peter S. Lee", "Andrew B. Ward", "Ian A. Wilson", "Ashley Dagley", "Donald F. Smee", "David Baker", "Deborah Heydenburg Fuller"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005409.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Intranasal_delivery_of_HB36_6_affords_therapeutic_protection_against_lethal_challenge_by_influenza_virus_/2602132", "title"=>"Intranasal delivery of HB36.6 affords therapeutic protection against lethal challenge by influenza virus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-04 21:26:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/4251049"], "description"=>"<p>(a) Viral titers in nasal washes of untreated infected controls (Ctr) and mice that received 6.0 mg/kg HB36.6 either 1 day before (Prophylaxis, Pro) or 1 day after (Therapeutic, Ther) infection with 10 MLD<sub>50</sub> CA09 virus. Nasal washes collected on days 2, 4 and 6 post-infection were measured by determining the 50% tissue culture infectious dose (TCID<sub>50</sub>) (bars indicate mean viral titer ±SD, n = 18 mice per group, three replicate experiments). (b) IHC staining of intracellular influenza NP (H1N1) of representative lung sections from uninfected (Naïve) and untreated infected controls (Control) and HB36.6-treated mice (Prophylactic and Therapeutic) at 4 days post-infection with 10 MLD<sub>50</sub> CA09 virus. Mouse lungs were not inflated with formalin and consequently resulted in lung collapse and a more hypercellular appearance in the uninfected control. Images selected show representative staining of influenza (NP) positive cells for each group. (c) Quantification of influenza positive cells in lung tissues was performed by measuring the area of positive staining compared to the total tissue on the slide (uniform random sampling of 50% lung tissue). (d) Inflammatory cytokines were assayed by Bio-Plex using supernatants from lung homogenates obtained from BALB/c mice on day 2 following infection with 10 MLD<sub>50</sub> CA09 virus (n = 8 mice per group). The fold change over naïve-uninfected mice is shown. For a, c and d, significant differences between the Pro and Ther groups to the Ctr group are shown: *P < 0.05, **P < 0.001.</p>", "links"=>[], "tags"=>["influenza", "binding", "dose", "protein", "HA", "computationally", "host", "infection", "HB 36.6", "response", "mg", "region", "Host Immune Response", "protection", "challenge"], "article_id"=>2602135, "categories"=>["Biochemistry", "Medicine", "Microbiology", "Molecular Biology", "Pharmacology", "Immunology", "Biological Sciences not elsewhere classified", "Infectious Diseases", "Virology", "Computational Biology"], "users"=>["Merika Treants Koday", "Jorgen Nelson", "Aaron Chevalier", "Michael Koday", "Hannah Kalinoski", "Lance Stewart", "Lauren Carter", "Travis Nieusma", "Peter S. Lee", "Andrew B. Ward", "Ian A. Wilson", "Ashley Dagley", "Donald F. Smee", "David Baker", "Deborah Heydenburg Fuller"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005409.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/HB36_6_suppresses_viral_replication_and_inflammation_in_the_lung_/2602135", "title"=>"HB36.6 suppresses viral replication and inflammation in the lung.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-04 21:26:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/4250998"], "description"=>"<p>(a) Crystal structure of A/South Carolina/1/1918 (H1) HA (derived from PDB 3R2X) filtered to 20 Å resolution. (b) Negative-stain EM reconstruction of PR8 HA bound to HB36.6. (c) X-ray structure of A/South Carolina/1/1918 (H1) HA (PDB 3R2X) (blue) in complex with HB36.6 (cyan) docked into PR8 EM reconstruction in b. HB36.6 fits well into the extra density in the stem region. (d) Equilibrium binding constants determined by biolayer interferometry for HB36.5 and HB36.6 against six HAs demonstrate broad improvements against a variety of Group 1 subtypes. (e) EC<sub>50</sub> (μg/ml), compound concentration that reduces viral replication by 50%, of HB36.6, the monoclonal antibody FI6v3, and ribavirin against five representative strains from H1, H9, and H5 Group 1 viruses and two H3 Group 2 viruses. ND: not determined.</p>", "links"=>[], "tags"=>["influenza", "binding", "dose", "protein", "HA", "computationally", "host", "infection", "HB 36.6", "response", "mg", "region", "Host Immune Response", "protection", "challenge"], "article_id"=>2602105, "categories"=>["Biochemistry", "Medicine", "Microbiology", "Molecular Biology", "Pharmacology", "Immunology", "Biological Sciences not elsewhere classified", "Infectious Diseases", "Virology", "Computational Biology"], "users"=>["Merika Treants Koday", "Jorgen Nelson", "Aaron Chevalier", "Michael Koday", "Hannah Kalinoski", "Lance Stewart", "Lauren Carter", "Travis Nieusma", "Peter S. Lee", "Andrew B. Ward", "Ian A. Wilson", "Ashley Dagley", "Donald F. Smee", "David Baker", "Deborah Heydenburg Fuller"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005409.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Characterization_of_HB36_6_/2602105", "title"=>"Characterization of HB36.6.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-04 21:26:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/4251061"], "description"=>"<p>(a) Inflammatory cytokines were assayed by Bio-Plex using supernatants from lung homogenates obtained from BALB/c mice 2, 24 and 48 hours following administration with HB36.6 (6.0 mg/kg) or the scaffold protein (PDB ID 1u84) (6.0 mg/kg) (n = 10 mice per group). Fold change over naïve mice is shown. *P < 0.05. (b) Survival and weight change in SCID and MyD88-/- mice (n = 10 per group) that received 6.0 mg/kg of HB36.6, scaffold protein, or Protein Ctr (lysozyme) IN 2 hours before IN infection with 10 MLD<sub>50</sub> CA09 virus.</p>", "links"=>[], "tags"=>["influenza", "binding", "dose", "protein", "HA", "computationally", "host", "infection", "HB 36.6", "response", "mg", "region", "Host Immune Response", "protection", "challenge"], "article_id"=>2602138, "categories"=>["Biochemistry", "Medicine", "Microbiology", "Molecular Biology", "Pharmacology", "Immunology", "Biological Sciences not elsewhere classified", "Infectious Diseases", "Virology", "Computational Biology"], "users"=>["Merika Treants Koday", "Jorgen Nelson", "Aaron Chevalier", "Michael Koday", "Hannah Kalinoski", "Lance Stewart", "Lauren Carter", "Travis Nieusma", "Peter S. Lee", "Andrew B. Ward", "Ian A. Wilson", "Ashley Dagley", "Donald F. Smee", "David Baker", "Deborah Heydenburg Fuller"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005409.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/HB36_6_induces_a_transient_cytokine_response_that_is_not_required_for_protection_/2602138", "title"=>"HB36.6 induces a transient cytokine response that is not required for protection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-04 21:26:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/4251016"], "description"=>"<p>(a) Survival and weight change in BALB/c mice (n = 10 per group) that received 6.0 mg/kg of HB36.6 administered intranasally (IN) at 2, 24, or 48 hours before challenge with 10 MLD<sub>50</sub> CA09 virus. The Protein Control (Ctr) group received 6.0 mg/kg of lysozyme at 2 or 48 hours before challenge with 10 MLD<sub>50</sub> CA09 virus. (b) Survival and weight change in BALB/c mice (n = 5 per group) that received 0.01–1 mg/kg IN doses of HB36.6 2 hours before challenge with 10 MLD<sub>50</sub> of CA09 virus. (c) Survival and weight change in BALB/c mice (n = 10 per group) that received 3.0 mg/kg of HB36.6 IN 2 hours before IN infection with 10 MLD<sub>50</sub> of H1N1 CA09 virus, 6 MLD<sub>50</sub> H1N1 A/PR/8/34 (PR8), or 3 MLD<sub>50</sub> of H5N1 A/Duck/MN/1525/81 (MN81) virus. Mean and SEM are shown.</p>", "links"=>[], "tags"=>["influenza", "binding", "dose", "protein", "HA", "computationally", "host", "infection", "HB 36.6", "response", "mg", "region", "Host Immune Response", "protection", "challenge"], "article_id"=>2602123, "categories"=>["Biochemistry", "Medicine", "Microbiology", "Molecular Biology", "Pharmacology", "Immunology", "Biological Sciences not elsewhere classified", "Infectious Diseases", "Virology", "Computational Biology"], "users"=>["Merika Treants Koday", "Jorgen Nelson", "Aaron Chevalier", "Michael Koday", "Hannah Kalinoski", "Lance Stewart", "Lauren Carter", "Travis Nieusma", "Peter S. Lee", "Andrew B. Ward", "Ian A. Wilson", "Ashley Dagley", "Donald F. Smee", "David Baker", "Deborah Heydenburg Fuller"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005409.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Intranasal_delivery_of_HB36_6_affords_prophylactic_protection_against_lethal_challenge_by_influenza_virus_/2602123", "title"=>"Intranasal delivery of HB36.6 affords prophylactic protection against lethal challenge by influenza virus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-04 21:26:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/4250989"], "description"=>"<p>(<b>a</b>) HB36.5, in complex with HA, colored by average residue enrichment in FACS sorts against 7 different HA subtypes. Final residue identity after mutagenesis and selection to obtain HB36.6 are labeled in black. Positions 54, 64, and 68 retained their HB36.5 identities. (<b>b</b>) Enrichment of substitutions at 12 key positions in HB36.5 in selections against each HA strain. Labels at the bottom indicate position in HB36.5; numbers at the top represent the different flu strains and subtypes (1: A/South Carolina/1/1918 (H1), 2: A/California/04/2009 (H1), 3: A/Vietnam/1203/2004 (H5), 4: A/Indonesia/05/2005 (H5), 5: A/Adachi/2/1957 (H2), 6: A/turkey/Wisconsin/1/1966 (H9), 7: A/duck/Alberta/60/1976 (H12)). At most positions, the enrichment profiles against the different HA strains are similar but, at several positions, they are quite distinct. At position 54, for example, arginine is highly conserved and substitutable for lysine in selections for binding against HAs 1–4, but is outcompeted by smaller charged/polar residues in selections against HAs 5–7 (red region at upper right of R54 panel). White cells indicate insufficient data (<15 sequences in the input library) and black boxes indicate the residue identities in HB36.6. (<b>c</b>) Origin of HA strain dependence of substitutions at HB36.5 position R54. Arg54 forms a hydrogen bond network with Asp and Arg residues in HAs 1–4. In HAs 5–7, the Asp is substituted by a Glu, disrupting the interface with Arg54 leading to a preference for smaller polar residues.</p>", "links"=>[], "tags"=>["influenza", "binding", "dose", "protein", "HA", "computationally", "host", "infection", "HB 36.6", "response", "mg", "region", "Host Immune Response", "protection", "challenge"], "article_id"=>2602093, "categories"=>["Biochemistry", "Medicine", "Microbiology", "Molecular Biology", "Pharmacology", "Immunology", "Biological Sciences not elsewhere classified", "Infectious Diseases", "Virology", "Computational Biology"], "users"=>["Merika Treants Koday", "Jorgen Nelson", "Aaron Chevalier", "Michael Koday", "Hannah Kalinoski", "Lance Stewart", "Lauren Carter", "Travis Nieusma", "Peter S. Lee", "Andrew B. Ward", "Ian A. Wilson", "Ashley Dagley", "Donald F. Smee", "David Baker", "Deborah Heydenburg Fuller"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005409.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Specificity_enhancing_mutations_and_overall_affinity_increasing_substitutions_using_selection_against_different_HA_subtypes_/2602093", "title"=>"Specificity-enhancing mutations and overall affinity-increasing substitutions using selection against different HA subtypes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-04 21:26:34"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"42", "full-text"=>"43", "pdf"=>"17", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"30", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"43", "full-text"=>"35", "pdf"=>"21", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"27", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"31", "full-text"=>"33", "pdf"=>"16", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"13", "full-text"=>"15", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"13", "full-text"=>"15", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"24", "full-text"=>"26", "pdf"=>"16", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"17", "full-text"=>"14", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"20", "full-text"=>"20", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"16", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"35", "full-text"=>"34", "pdf"=>"16", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"27", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"12", "full-text"=>"11", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"30", "full-text"=>"14", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"35", "supp-data"=>"4", "cited-by"=>"1", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"16", "full-text"=>"15", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"18", "full-text"=>"14", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"14", "full-text"=>"19", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"18", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"16", "full-text"=>"16", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"17", "full-text"=>"14", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"19", "full-text"=>"20", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"14", "full-text"=>"14", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"21", "full-text"=>"20", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"14", "full-text"=>"21", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"16", "full-text"=>"22", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"18", "full-text"=>"20", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"1", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"14", "full-text"=>"11", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"14", "full-text"=>"10", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"14", "full-text"=>"12", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"21", "full-text"=>"22", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"12", "full-text"=>"7", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"14", "full-text"=>"9", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"22", "full-text"=>"19", "pdf"=>"10", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"18", "full-text"=>"14", "pdf"=>"8", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"16", "full-text"=>"26", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}

Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}

F1000Prime | Further Information

Loading … Spinner
There are currently no alerts