| Intranasal immunization with influenza VLPs incorporating membrane-anchored flagellin induces strong heterosubtypic protection. | |
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MedLine Citation:
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PMID: 21124769 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We demonstrated previously that the incorporation of a membrane-anchored form of flagellin into influenza virus-like particles (VLPs) improved the immunogenicity of VLPs significantly, inducing partially protective heterosubtypic immunity by intramuscular immunization. Because the efficacy of mucosal vaccination is highly dependent on an adjuvant, and is particularly effective for preventing mucosal infections such as influenza, we determined whether the membrane-anchored flagellin is an efficient adjuvant for VLP vaccines by a mucosal immunization route. We compared the adjuvant effect of membrane-anchored and soluble flagellins for immunization with influenza A/PR8 (H1N1) VLPs by the intranasal route in a mouse model. The results demonstrate that membrane-anchored flagellin is an effective adjuvant for intranasal (IN) immunization, inducing enhanced systemic and mucosal antibody responses. High cellular responses were also observed as shown by cytokine production in splenocyte cultures when stimulated with viral antigens. All mice immunized with flagellin-containing VLPs survived challenge with a high lethal dose of homologous virus as well as a high dose heterosubtypic virus challenge (40 LD(50) of A/Philippines/82, H3N2). In contrast, no protection was observed with a standard HA/M1 VLP group upon heterosubtypic challenge. Soluble flagellin exhibited a moderate adjuvant effect when co-administered with VLPs by the mucosal route, as indicated by enhanced systemic and mucosal responses and partial heterosubtypic protection. The membrane-anchored form of flagellin incorporated together with antigen into influenza VLPs is effective as an adjuvant by the mucosal route and unlike standard VLPs, immunization with such chimeric VLPs elicits protective immunity to challenge with a distantly related influenza A virus. |
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Authors:
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Bao-Zhong Wang; Rui Xu; Fu-Shi Quan; Sang-Moo Kang; Li Wang; Richard W Compans |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-11-29 |
Journal Detail:
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Title: PloS one Volume: 5 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2010 |
Date Detail:
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Created Date: 2010-12-02 Completed Date: 2011-04-27 Revised Date: 2013-03-05 |
Medline Journal Info:
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Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
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Languages: eng Pagination: e13972 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Intranasal Animals Antibodies, Viral / blood, immunology Cell Line Cell Membrane / metabolism Chick Embryo Flagellin / genetics, immunology*, metabolism Hemagglutination Tests Immunity, Mucosal / drug effects, immunology Immunization / methods Influenza A Virus, H1N1 Subtype / genetics, immunology Influenza A Virus, H3N2 Subtype / genetics, immunology Influenza Vaccines / administration & dosage, immunology* Interferon-gamma / metabolism Interleukin-4 / metabolism Mice Neutralization Tests Orthomyxoviridae Infections / immunology*, prevention & control, virology Spodoptera T-Lymphocytes / drug effects, immunology, metabolism Virion / genetics, immunology* |
| Grant Support | |
ID/Acronym/Agency:
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AI068003/AI/NIAID NIH HHS; AI074579/AI/NIAID NIH HHS; R01 AI068003-01/AI/NIAID NIH HHS; U01 AI074579-01/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Viral; 0/Influenza Vaccines; 12777-81-0/Flagellin; 207137-56-2/Interleukin-4; 82115-62-6/Interferon-gamma |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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