An Adenoviral Vector-Based Mucosal Vaccine Is Effective in Protection Against Botulism

Gene Ther. 2009 Mar;16(3):367-75. doi: 10.1038/gt.2008.181. Epub 2009 Jan 8.

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.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Antibodies, Bacterial / biosynthesis
  • Bacterial Vaccines / immunology*
  • Botulinum Toxins / immunology*
  • Botulism / immunology
  • Botulism / 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

Substances

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