1. ¹Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
2. ²Department of Medicine and Department of Biochemistry and Molecular Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA
3. ³Integrated Toxicology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, USA

Correspondence: Dr M Zeng, Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 672, Rochester, New York 14642, USA. E-mail: Mingtao_Zeng@urmc.rochester.edu

Received 10 July 2008; Revised 22 October 2008; Accepted 3 November 2008; Published online 8 January 2009.

Abstract

A replication-incompetent adenoviral vector encoding the heavy chain C-fragment (H_C50) of botulinum neurotoxin type C (BoNT/C) was evaluated as a mucosal vaccine against botulism in a mouse model. Single intranasal inoculation of the adenoviral vector elicited a high level of H_C50-specific IgG, IgG1 and IgG2a in sera and IgA in mucosal secretions as early as 2 weeks after vaccination. The antigen-specific serum antibodies were maintained at a high level at least until the 27th week. Immune sera showed high potency in neutralizing BoNT/C as indicated by in vitro toxin neutralization assay. The mice receiving single dose of 2 10⁷ p.f.u. (plaque-forming unit) of adenoviral vector were completely protected against challenge with up to 10⁴ MLD₅₀ of BoNT/C. The protective immunity showed vaccine dose dependence from 10⁵ to 2 10⁷ p.f.u. of adenoviral vector. In addition, animals receiving single intranasal dose of 2 10⁷ p.f.u. adenoviral vector could be protected against 100 MLD₅₀ 27 weeks after vaccination. Animals with preexisting immunity to adenovirus could also be vaccinated intranasally and protected against lethal challenge with BoNT/C. These results suggest that the adenoviral vector is a highly effective gene-based mucosal vaccine against botulism.