Abstract
A replication-incompetent adenoviral vector encoding the heavy chain C-fragment (HC50) 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 HC50-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.
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