Assessment of Influenza Virus Hemagglutinin Stalk-Based Immunity in Ferrets

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Published inJournal of Virology Vol. 88; no. 6; pp. 3432 - 3442
Main Authors Krammer, Florian, Hai, Rong, Yondola, Mark, Tan, Gene S, Leyva-Grado, Victor H, Ryder, Alex B, Miller, Matthew S, Rose, John K, Palese, Peter, García-Sastre, Adolfo, Albrecht, Randy A
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 01.03.2014
Subjects
Animals
Antibodies, Neutralizing - immunology
Antibodies, Viral - immunology
Disease Models, Animal
Ferrets
Hemagglutinin Glycoproteins, Influenza Virus - administration & dosage
Hemagglutinin Glycoproteins, Influenza Virus - chemistry
Hemagglutinin Glycoproteins, Influenza Virus - genetics
Hemagglutinin Glycoproteins, Influenza Virus - immunology
Hemagglutinins
Humans
Influenza A Virus, H1N1 Subtype - genetics
Influenza A Virus, H1N1 Subtype - immunology
Influenza Vaccines - administration & dosage
Influenza Vaccines - chemistry
Influenza Vaccines - genetics
Influenza Vaccines - immunology
Influenza virus
Influenza, Human - immunology
Influenza, Human - prevention & control
Influenza, Human - virology
Male
Mustela
Protein Structure, Tertiary
Vaccines and Antiviral Agents
Online AccessGet full text

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Abstract Classifications Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to JVI .asm.org, visit: JVI       
AbstractList Therapeutic monoclonal antibodies that target the conserved stalk domain of the influenza virus hemagglutinin and stalk-based universal influenza virus vaccine strategies are being developed as promising countermeasures for influenza virus infections. The pan-H1-reactive monoclonal antibody 6F12 has been extensively characterized and shows broad efficacy against divergent H1N1 strains in the mouse model. Here we demonstrate its efficacy against a pandemic H1N1 challenge virus in the ferret model of influenza disease. Furthermore, we recently developed a universal influenza virus vaccine strategy based on chimeric hemagglutinin constructs that focuses the immune response on the conserved stalk domain of the hemagglutinin. Here we set out to test this vaccination strategy in the ferret model. Both strategies, pretreatment of animals with a stalk-reactive monoclonal antibody and vaccination with chimeric hemagglutinin-based constructs, were able to significantly reduce viral titers in nasal turbinates, lungs, and olfactory bulbs. In addition, vaccinated animals also showed reduced nasal wash viral titers. In summary, both strategies showed efficacy in reducing viral loads after an influenza virus challenge in the ferret model. IMPORTANCE Influenza virus hemagglutinin stalk-reactive antibodies tend to be less potent yet are more broadly reactive and can neutralize seasonal and pandemic influenza virus strains. The ferret model was used to assess the potential of hemagglutinin stalk-based immunity to provide protection against influenza virus infection. The novelty and significance of the findings described in this report support the development of vaccines stimulating stalk-specific antibody responses.
Therapeutic monoclonal antibodies that target the conserved stalk domain of the influenza virus hemagglutinin and stalk-based universal influenza virus vaccine strategies are being developed as promising countermeasures for influenza virus infections. The pan-H1-reactive monoclonal antibody 6F12 has been extensively characterized and shows broad efficacy against divergent H1N1 strains in the mouse model. Here we demonstrate its efficacy against a pandemic H1N1 challenge virus in the ferret model of influenza disease. Furthermore, we recently developed a universal influenza virus vaccine strategy based on chimeric hemagglutinin constructs that focuses the immune response on the conserved stalk domain of the hemagglutinin. Here we set out to test this vaccination strategy in the ferret model. Both strategies, pretreatment of animals with a stalk-reactive monoclonal antibody and vaccination with chimeric hemagglutinin-based constructs, were able to significantly reduce viral titers in nasal turbinates, lungs, and olfactory bulbs. In addition, vaccinated animals also showed reduced nasal wash viral titers. In summary, both strategies showed efficacy in reducing viral loads after an influenza virus challenge in the ferret model. IMPORTANCE Influenza virus hemagglutinin stalk-reactive antibodies tend to be less potent yet are more broadly reactive and can neutralize seasonal and pandemic influenza virus strains. The ferret model was used to assess the potential of hemagglutinin stalk-based immunity to provide protection against influenza virus infection. The novelty and significance of the findings described in this report support the development of vaccines stimulating stalk-specific antibody responses.
Classifications Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to JVI .asm.org, visit: JVI       
Therapeutic monoclonal antibodies that target the conserved stalk domain of the influenza virus hemagglutinin and stalk-based universal influenza virus vaccine strategies are being developed as promising countermeasures for influenza virus infections. The pan-H1-reactive monoclonal antibody 6F12 has been extensively characterized and shows broad efficacy against divergent H1N1 strains in the mouse model. Here we demonstrate its efficacy against a pandemic H1N1 challenge virus in the ferret model of influenza disease. Furthermore, we recently developed a universal influenza virus vaccine strategy based on chimeric hemagglutinin constructs that focuses the immune response on the conserved stalk domain of the hemagglutinin. Here we set out to test this vaccination strategy in the ferret model. Both strategies, pretreatment of animals with a stalk-reactive monoclonal antibody and vaccination with chimeric hemagglutinin-based constructs, were able to significantly reduce viral titers in nasal turbinates, lungs, and olfactory bulbs. In addition, vaccinated animals also showed reduced nasal wash viral titers. In summary, both strategies showed efficacy in reducing viral loads after an influenza virus challenge in the ferret model. Influenza virus hemagglutinin stalk-reactive antibodies tend to be less potent yet are more broadly reactive and can neutralize seasonal and pandemic influenza virus strains. The ferret model was used to assess the potential of hemagglutinin stalk-based immunity to provide protection against influenza virus infection. The novelty and significance of the findings described in this report support the development of vaccines stimulating stalk-specific antibody responses.
Therapeutic monoclonal antibodies that target the conserved stalk domain of the influenza virus hemagglutinin and stalk-based universal influenza virus vaccine strategies are being developed as promising countermeasures for influenza virus infections. The pan-H1-reactive monoclonal antibody 6F12 has been extensively characterized and shows broad efficacy against divergent H1N1 strains in the mouse model. Here we demonstrate its efficacy against a pandemic H1N1 challenge virus in the ferret model of influenza disease. Furthermore, we recently developed a universal influenza virus vaccine strategy based on chimeric hemagglutinin constructs that focuses the immune response on the conserved stalk domain of the hemagglutinin. Here we set out to test this vaccination strategy in the ferret model. Both strategies, pretreatment of animals with a stalk-reactive monoclonal antibody and vaccination with chimeric hemagglutinin-based constructs, were able to significantly reduce viral titers in nasal turbinates, lungs, and olfactory bulbs. In addition, vaccinated animals also showed reduced nasal wash viral titers. In summary, both strategies showed efficacy in reducing viral loads after an influenza virus challenge in the ferret model.UNLABELLEDTherapeutic monoclonal antibodies that target the conserved stalk domain of the influenza virus hemagglutinin and stalk-based universal influenza virus vaccine strategies are being developed as promising countermeasures for influenza virus infections. The pan-H1-reactive monoclonal antibody 6F12 has been extensively characterized and shows broad efficacy against divergent H1N1 strains in the mouse model. Here we demonstrate its efficacy against a pandemic H1N1 challenge virus in the ferret model of influenza disease. Furthermore, we recently developed a universal influenza virus vaccine strategy based on chimeric hemagglutinin constructs that focuses the immune response on the conserved stalk domain of the hemagglutinin. Here we set out to test this vaccination strategy in the ferret model. Both strategies, pretreatment of animals with a stalk-reactive monoclonal antibody and vaccination with chimeric hemagglutinin-based constructs, were able to significantly reduce viral titers in nasal turbinates, lungs, and olfactory bulbs. In addition, vaccinated animals also showed reduced nasal wash viral titers. In summary, both strategies showed efficacy in reducing viral loads after an influenza virus challenge in the ferret model.Influenza virus hemagglutinin stalk-reactive antibodies tend to be less potent yet are more broadly reactive and can neutralize seasonal and pandemic influenza virus strains. The ferret model was used to assess the potential of hemagglutinin stalk-based immunity to provide protection against influenza virus infection. The novelty and significance of the findings described in this report support the development of vaccines stimulating stalk-specific antibody responses.IMPORTANCEInfluenza virus hemagglutinin stalk-reactive antibodies tend to be less potent yet are more broadly reactive and can neutralize seasonal and pandemic influenza virus strains. The ferret model was used to assess the potential of hemagglutinin stalk-based immunity to provide protection against influenza virus infection. The novelty and significance of the findings described in this report support the development of vaccines stimulating stalk-specific antibody responses.
Author Gene S. Tan
Rong Hai
John K. Rose
Randy A. Albrecht
Matthew S. Miller
Alex B. Ryder
Mark Yondola
Florian Krammer
Adolfo García-Sastre
Peter Palese
Victor H. Leyva-Grado
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  surname: Albrecht
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/24403585$$D View this record in MEDLINE/PubMed
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Present address: Mark Yondola, Avatar Biotechnologies, Brooklyn, NY.
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PublicationDate 2014-03-01
PublicationDateYYYYMMDD 2014-03-01
PublicationDate_xml – month: 03
  year: 2014
  text: 2014-03-01
  day: 01
PublicationDecade 2010
PublicationPlace United States
PublicationPlace_xml – name: United States
– name: 1752 N St., N.W., Washington, DC
PublicationTitle Journal of Virology
PublicationTitleAlternate J Virol
PublicationYear 2014
Publisher American Society for Microbiology
Publisher_xml – name: American Society for Microbiology
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Therapeutic monoclonal antibodies that target the conserved stalk domain of the influenza virus hemagglutinin and stalk-based universal influenza virus vaccine...
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SubjectTerms Animals
Antibodies, Neutralizing - immunology
Antibodies, Viral - immunology
Disease Models, Animal
Ferrets
Hemagglutinin Glycoproteins, Influenza Virus - administration & dosage
Hemagglutinin Glycoproteins, Influenza Virus - chemistry
Hemagglutinin Glycoproteins, Influenza Virus - genetics
Hemagglutinin Glycoproteins, Influenza Virus - immunology
Hemagglutinins
Humans
Influenza A Virus, H1N1 Subtype - genetics
Influenza A Virus, H1N1 Subtype - immunology
Influenza Vaccines - administration & dosage
Influenza Vaccines - chemistry
Influenza Vaccines - genetics
Influenza Vaccines - immunology
Influenza virus
Influenza, Human - immunology
Influenza, Human - prevention & control
Influenza, Human - virology
Male
Mustela
Protein Structure, Tertiary
Vaccines and Antiviral Agents
Title Assessment of Influenza Virus Hemagglutinin Stalk-Based Immunity in Ferrets
URI http://jvi.asm.org/content/88/6/3432.abstract
https://www.ncbi.nlm.nih.gov/pubmed/24403585
https://www.proquest.com/docview/1502326472
https://www.proquest.com/docview/1508758406
https://pubmed.ncbi.nlm.nih.gov/PMC3957929
Volume 88
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