Detoxification of the Helicobacter pylori cytotoxin.
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.
Manetti
R
R
IRIS, Chiron-Vaccines, Siena, Italy.
Massari
P
P
Marchetti
M
M
Magagnoli
C
C
Nuti
S
S
Lupetti
P
P
Ghiara
P
P
Rappuoli
R
R
Telford
J L
JL
D000818:Animals; D001426:Bacterial Proteins / Q000633:toxicity*; D001428:Bacterial Vaccines / Q000276:immunology; D003603:Cytotoxins / Q000378:metabolism / Q000633:toxicity*; D005557:Formaldehyde / Q000494:pharmacology; D006367:HeLa Cells; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits
D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D003603:Cytotoxins; C074689:VacA protein, Helicobacter pylori; D005557:Formaldehyde