An adenoviral vector-based mucosal vaccine is effective in protection against botulism.
A replication-incompetent adenoviral vector encoding the heavy chain C-fragment (H(C)50) 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(C)50-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 x 10(7) p.f.u. (plaque-forming unit) of adenoviral vector were completely protected against challenge with up to 10(4) x MLD(50) of BoNT/C. The protective immunity showed vaccine dose dependence from 10(5) to 2 x 10(7) p.f.u. of adenoviral vector. In addition, animals receiving single intranasal dose of 2 x 10(7) p.f.u. adenoviral vector could be protected against 100 x MLD(50) 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.
Xu
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Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Pichichero
M E
ME
Simpson
L L
LL
Elias
Md
M
Smith
L A
LA
Zeng
M
M
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001428:Bacterial Vaccines / Q000276:immunology*; D001905:Botulinum Toxins / Q000276:immunology*; D001906:Botulism / Q000276:immunology / Q000517:prevention & control*; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005822:Genetic Vectors; D018928:Immunity, Mucosal; D051379:Mice; D008807:Mice, Inbred BALB C; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000276:immunology
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D014614:Vaccines, Synthetic; D001905:Botulinum Toxins; C096324:botulinum toxin type C