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A novel neurotoxoid vaccine prevents mucosal botulism.

Publication ,  Journal Article
Kobayashi, R; Kohda, T; Kataoka, K; Ihara, H; Kozaki, S; Pascual, DW; Staats, HF; Kiyono, H; McGhee, JR; Fujihashi, K
Published in: J Immunol
February 15, 2005

The threat posed by botulism, classically a food- and waterborne disease with a high morbidity and mortality, has increased exponentially in an age of bioterrorism. Because botulinum neurotoxin (BoNT) could be easily disseminated by terrorists using an aerosol or could be used to contaminate the food or water supply, the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases has classified it as a category A agent. Although clearly the development of a safe and effective mucosal vaccine against this toxin should be a high priority, essentially no studies to date have assessed mucosal immune responses to this disease. To bridge this gap in our knowledge, we immunized mice weekly for 4 wk with nasal doses of BoNT type A toxoid and a mutant of cholera toxin termed E112K. We found elevated levels of BoNT-specific IgG Abs in plasma and of secretory IgA Abs in external secretions (nasal washes, saliva, and fecal extracts). When mice given nasal BoNT vaccine were challenged with 4 x 10(3) LD50 of BoNT type A (BoNT/A) via the i.p. route, complete protection was seen, while naive mice given the same dosage died within 2 h. To further confirm the efficacy of this nasal BoNT vaccine, an oral LD50 was determined. When mice were given an oral challenge of 5 microg (2 x oral LD50) of progenitor BoNT/A, all immunized mice survived beyond 5 days, while nonimmunized mice did not. The fecal extract samples from nasally vaccinated mice were found to contain neutralizing secretory IgA Abs. Taken together, these results show that nasal BoNT/A vaccine effectively prevents mucosal BoNT intoxication.

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Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

February 15, 2005

Volume

174

Issue

4

Start / End Page

2190 / 2195

Location

United States

Related Subject Headings

  • Toxoids
  • Nasal Mucosa
  • Mice, Inbred C57BL
  • Mice
  • Intestinal Mucosa
  • Immunology
  • Immunoglobulin A, Secretory
  • Immunity, Innate
  • Clostridium botulinum type A
  • Botulism
 

Citation

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Kobayashi, R., Kohda, T., Kataoka, K., Ihara, H., Kozaki, S., Pascual, D. W., … Fujihashi, K. (2005). A novel neurotoxoid vaccine prevents mucosal botulism. J Immunol, 174(4), 2190–2195. https://doi.org/10.4049/jimmunol.174.4.2190
Kobayashi, Ryoki, Tomoko Kohda, Kosuke Kataoka, Hideshi Ihara, Shunji Kozaki, David W. Pascual, Herman F. Staats, Hiroshi Kiyono, Jerry R. McGhee, and Kohtaro Fujihashi. “A novel neurotoxoid vaccine prevents mucosal botulism.J Immunol 174, no. 4 (February 15, 2005): 2190–95. https://doi.org/10.4049/jimmunol.174.4.2190.
Kobayashi R, Kohda T, Kataoka K, Ihara H, Kozaki S, Pascual DW, et al. A novel neurotoxoid vaccine prevents mucosal botulism. J Immunol. 2005 Feb 15;174(4):2190–5.
Kobayashi, Ryoki, et al. “A novel neurotoxoid vaccine prevents mucosal botulism.J Immunol, vol. 174, no. 4, Feb. 2005, pp. 2190–95. Pubmed, doi:10.4049/jimmunol.174.4.2190.
Kobayashi R, Kohda T, Kataoka K, Ihara H, Kozaki S, Pascual DW, Staats HF, Kiyono H, McGhee JR, Fujihashi K. A novel neurotoxoid vaccine prevents mucosal botulism. J Immunol. 2005 Feb 15;174(4):2190–2195.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

February 15, 2005

Volume

174

Issue

4

Start / End Page

2190 / 2195

Location

United States

Related Subject Headings

  • Toxoids
  • Nasal Mucosa
  • Mice, Inbred C57BL
  • Mice
  • Intestinal Mucosa
  • Immunology
  • Immunoglobulin A, Secretory
  • Immunity, Innate
  • Clostridium botulinum type A
  • Botulism