Email updates

Keep up to date with the latest news and content from BMC Immunology and BioMed Central.

Open Access Research article

Adenovirus F protein as a delivery vehicle for botulinum B

Beata Clapp1, Sarah Golden1, Massimo Maddaloni1, Herman F Staats2 and David W Pascual1*

Author Affiliations

1 Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717-3610, USA

2 Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA

For all author emails, please log on.

BMC Immunology 2010, 11:36  doi:10.1186/1471-2172-11-36

Published: 7 July 2010

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, 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 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 immunogens are highly immunogenic, especially when genetically fused to Ad2F, and Ad2F can be exploited as a vaccine delivery platform to the mucosa.