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adenovirus f protein as a delivery vehicle for botulinum b腺病毒f蛋白作为肉毒杆菌b的运载工具
Clapp et al. BMC Immunology 2010, 11:36
/1471-2172/11/36
R E S E A R C H A R T I C L E Open Access
Research article
Adenovirus F protein as a delivery vehicle for
botulinum B
1 1 1 2 1
Beata Clapp , Sarah Golden , Massimo Maddaloni , Herman F Staats and David W Pascual*
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
β-trefoil domain (Hcβtre), we hypothesize that immunization with the Hcβtre 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 Hcβtre serotype B immunogen was genetically fused to Ad2F (Hcβtre/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 Hcβtre-Ad2F relative to Hcβtre alone; however, simi lar 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 Hcβtre-immunized mice that showed more mixed Th1 and Th2
cells. Using a mouse neutralization assay, sera from animals immunized with Hcβtre and Hcβtre-Ad2F protected mice
against 2.0 LD50.
Conclusion: These results demonstrate that Hcβtre-based im
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