Adenovirus F protein as a delivery vehicle for botulinum B.

Published

Journal Article

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.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.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.

Full Text

Duke Authors

Cited Authors

  • Clapp, B; Golden, S; Maddaloni, M; Staats, HF; Pascual, DW

Published Date

  • July 7, 2010

Published In

Volume / Issue

  • 11 /

Start / End Page

  • 36 -

PubMed ID

  • 20609248

Pubmed Central ID

  • 20609248

Electronic International Standard Serial Number (EISSN)

  • 1471-2172

International Standard Serial Number (ISSN)

  • 1471-2172

Digital Object Identifier (DOI)

  • 10.1186/1471-2172-11-36

Language

  • eng