An adenoviral vector-based mucosal vaccine is effective in protection against botulism.

Abstract

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.

• Authors: Q Xu, M E Pichichero, L L Simpson, Md Elias, L A Smith, M Zeng
• Journal: Gene therapy (Gene Ther) Vol. 16 Issue 3 Pg. 367-75 (Mar 2009) ISSN: 1476-5462 [Electronic] England
• PMID: 19129860 (Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Bacterial
• Bacterial Vaccines
• Vaccines, Synthetic
• Botulinum Toxins
• botulinum toxin type C

Topics

• Adenoviridae (genetics)
• Animals
• Antibodies, Bacterial (biosynthesis)
• Bacterial Vaccines (immunology)
• Botulinum Toxins (immunology)
• Botulism (immunology, prevention & control)
• Dose-Response Relationship, Immunologic
• Enzyme-Linked Immunosorbent Assay (methods)
• Female
• Genetic Vectors
• Immunity, Mucosal
• Mice
• Mice, Inbred BALB C
• Vaccination (methods)
• Vaccines, Synthetic (immunology)