Authors:
Q Xu, M E Pichichero, L L Simpson, Md Elias, L A Smith, and M Zeng
Summary:
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.
Source:
Gene Therapy; (01/08/09)