Manetti R, Massari P, Marchetti M, Magagnoli C, Nuti S, Lupetti P, Ghiara P, Rappuoli R, Telford J L
IRIS, Chiron-Vaccines, Siena, Italy.
Infect Immun. 1997 Nov;65(11):4615-9. doi: 10.1128/iai.65.11.4615-4619.1997.
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.
用极低浓度的甲醛处理幽门螺杆菌空泡毒素，在HeLa细胞空泡形成试验和胃上皮损伤的体内试验中均导致毒性活性丧失。解毒对寡聚体或单体结构的完整性影响极小。类毒素保留了与靶细胞结合的能力，并在兔免疫后诱导产生高滴度的中和抗体。此外，用类毒素对小鼠进行口服免疫可使其免受适应小鼠的幽门螺杆菌菌株感染性攻击。毒素对甲醛处理的敏感性表明，蛋白质中的一些赖氨酸残基可能对毒性活性至关重要，以这种方式解毒的VacA可能是用于预防幽门螺杆菌感染和疾病的疫苗中的潜在候选物。
