Infect. Immun., 11 1997, 4615-4619, Vol 65, No. 11
Copyright © 1997, American Society for Microbiology

Detoxification of the Helicobacter pylori cytotoxin

R Manetti, P Massari, M Marchetti, C Magagnoli, S Nuti, P Lupetti, P Ghiara, R Rappuoli and JL Telford
IRIS, Chiron-Vaccines, Siena, Italy.

Treatment of the Helicobacter pylori vacuolating cytotoxin with very low concentrations of formaldehyde resulted in abrogation of toxic activity in both a HeLa cell vacuolation assay and an in vivo assay of gastric epithelial damage. Detoxification had only a minimal effect on the integrity of the oligomeric or monomeric structure. The toxoid retained the ability to bind to target cells and to induce high-titer neutralizing antibodies after immunization of rabbits. Furthermore, oral immunization of mice with the toxoid resulted in protection against infective challenge with mouse-adapted strains of H. pylori. The sensitivity of the toxin to formaldehyde treatment suggests that a few lysine residues in the protein may be essential for toxic activity and that VacA detoxified in this manner may be a potential candidate for inclusion in a vaccine against H. pylori infection and disease.

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