Show simple item record Clapp, B Golden, S Maddaloni, M Staats, HF Pascual, DW
dc.coverage.spatial England 2011-06-21T17:29:34Z 2010-07-07
dc.identifier 1471-2172-11-36
dc.identifier.citation BMC Immunol, 2010, 11 pp. 36 - ?
dc.description.abstract BACKGROUND: Immunization with recombinant carboxyl-terminal domain of the heavy chain (Hc domain) of botulinum neurotoxin (BoNT) stimulates protective immunity against native BoNT challenge. Most studies developing a botulism vaccine have focused on the whole Hc; however, since the principal protective epitopes are located within beta-trefoil domain (Hcbetatre), we hypothesize that immunization with the Hcbetatre domain is sufficient to confer protective immunity. In addition, enhancing its uptake subsequent to nasal delivery prompted development of an alternative vaccine strategy, and we hypothesize that the addition of targeting moiety adenovirus 2 fiber protein (Ad2F) may enhance such uptake during vaccination. RESULTS: The Hcbetatre serotype B immunogen was genetically fused to Ad2F (Hcbetatre/B-Ad2F), and its immunogenicity was tested in mice. In combination with the mucosal adjuvant, cholera toxin (CT), enhanced mucosal IgA and serum IgG Ab titers were induced by nasal Hcbetatre-Ad2F relative to Hcbetatre alone; however, similar Ab titers were obtained upon intramuscular immunization. These BoNT/B-specific Abs induced by nasal immunization were generally supported in large part by Th2 cells, as opposed to Hcbetatre-immunized mice that showed more mixed Th1 and Th2 cells. Using a mouse neutralization assay, sera from animals immunized with Hcbetatre and Hcbetatre-Ad2F protected mice against 2.0 LD50. CONCLUSION: These results demonstrate that Hcbetatre-based immunogens are highly immunogenic, especially when genetically fused to Ad2F, and Ad2F can be exploited as a vaccine delivery platform to the mucosa.
dc.format.extent 36 - ?
dc.language eng
dc.language.iso en_US en_US
dc.relation.ispartof BMC Immunol
dc.relation.isversionof 10.1186/1471-2172-11-36
dc.subject Adenoviridae
dc.subject Administration, Intranasal
dc.subject Animals
dc.subject B-Lymphocytes
dc.subject Botulinum Toxins
dc.subject Botulinum Toxins, Type A
dc.subject Botulism
dc.subject Cholera Toxin
dc.subject Cytokines
dc.subject Immunoassay
dc.subject Injections, Intramuscular
dc.subject Mice
dc.subject Mice, Inbred C57BL
dc.subject Neutralization Tests
dc.subject Protein Structure, Tertiary
dc.subject Recombinant Fusion Proteins
dc.subject Survival Analysis
dc.subject T-Lymphocytes, Helper-Inducer
dc.subject Vaccination
dc.subject Viral Proteins
dc.title Adenovirus F protein as a delivery vehicle for botulinum B.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US 2010-7-7 en_US
duke.description.endpage 36 en_US
duke.description.issue en_US
duke.description.startpage 36 en_US
duke.description.volume 11 en_US
dc.relation.journal Bmc Immunology en_US
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Immunology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pathology
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Human Vaccine Institute
pubs.publication-status Published online
pubs.volume 11
dc.identifier.eissn 1471-2172

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