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Adenovirus F protein as a delivery vehicle for botulinum B.

Publication ,  Journal Article
Clapp, B; Golden, S; Maddaloni, M; Staats, HF; Pascual, DW
Published in: BMC Immunol
July 7, 2010

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.

Duke Scholars

Published In

BMC Immunol

DOI

EISSN

1471-2172

Publication Date

July 7, 2010

Volume

11

Start / End Page

36

Location

England

Related Subject Headings

  • Viral Proteins
  • Vaccination
  • T-Lymphocytes, Helper-Inducer
  • Survival Analysis
  • Recombinant Fusion Proteins
  • Protein Structure, Tertiary
  • Neutralization Tests
  • Mice, Inbred C57BL
  • Mice
  • Injections, Intramuscular
 

Citation

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Clapp, B., Golden, S., Maddaloni, M., Staats, H. F., & Pascual, D. W. (2010). Adenovirus F protein as a delivery vehicle for botulinum B. BMC Immunol, 11, 36. https://doi.org/10.1186/1471-2172-11-36
Clapp, Beata, Sarah Golden, Massimo Maddaloni, Herman F. Staats, and David W. Pascual. “Adenovirus F protein as a delivery vehicle for botulinum B.BMC Immunol 11 (July 7, 2010): 36. https://doi.org/10.1186/1471-2172-11-36.
Clapp B, Golden S, Maddaloni M, Staats HF, Pascual DW. Adenovirus F protein as a delivery vehicle for botulinum B. BMC Immunol. 2010 Jul 7;11:36.
Clapp, Beata, et al. “Adenovirus F protein as a delivery vehicle for botulinum B.BMC Immunol, vol. 11, July 2010, p. 36. Pubmed, doi:10.1186/1471-2172-11-36.
Clapp B, Golden S, Maddaloni M, Staats HF, Pascual DW. Adenovirus F protein as a delivery vehicle for botulinum B. BMC Immunol. 2010 Jul 7;11:36.
Journal cover image

Published In

BMC Immunol

DOI

EISSN

1471-2172

Publication Date

July 7, 2010

Volume

11

Start / End Page

36

Location

England

Related Subject Headings

  • Viral Proteins
  • Vaccination
  • T-Lymphocytes, Helper-Inducer
  • Survival Analysis
  • Recombinant Fusion Proteins
  • Protein Structure, Tertiary
  • Neutralization Tests
  • Mice, Inbred C57BL
  • Mice
  • Injections, Intramuscular