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Helicobacter pylori cytotoxin: importance of native conformation for induction of neutralizing antibodies.

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  • 1. IRIS, Chiron-Biocine Immunobiological Research Institute Siena, Italy.
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    • Manetti R 1
    (1 author)

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Infection and Immunity, 01 Nov 1995, 63(11):4476-4480
https://doi.org/10.1128/iai.63.11.4476-4480.1995 PMID: 7591088 PMCID: PMC173637

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Abstract 

We have attempted to express the Helicobacter pylori vacuolating cytotoxin in Escherichia coli. Although the 95-kDa VacA polypeptide was expressed abundantly, it completely lacked any biological activity. In addition, this material failed to induce neutralizing antibodies after immunization of rabbits. In contrast, highly purified high-molecular-mass cytotoxin from the supernatant of H. pylori cultures was active in a HeLa cell assay and effectively induced a neutralizing response in rabbits. Neutralizing sera were shown to contain a high proportion of antibodies which recognized conformational epitopes found only on the native toxin. The data indicate that toxin-neutralizing epitopes are conformational and that potential vaccines based on the cytotoxin may benefit from the use of the intact molecule.

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Infect Immun. 1995 Nov; 63(11): 4476–4480.
PMCID: PMC173637
PMID: 7591088

Helicobacter pylori cytotoxin: importance of native conformation for induction of neutralizing antibodies.

R Manetti, P Massari, D Burroni, M de Bernard, A Marchini, R Olivieri, E Papini, C Montecucco, R Rappuoli, and J L Telford
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Abstract

We have attempted to express the Helicobacter pylori vacuolating cytotoxin in Escherichia coli. Although the 95-kDa VacA polypeptide was expressed abundantly, it completely lacked any biological activity. In addition, this material failed to induce neutralizing antibodies after immunization of rabbits. In contrast, highly purified high-molecular-mass cytotoxin from the supernatant of H. pylori cultures was active in a HeLa cell assay and effectively induced a neutralizing response in rabbits. Neutralizing sera were shown to contain a high proportion of antibodies which recognized conformational epitopes found only on the native toxin. The data indicate that toxin-neutralizing epitopes are conformational and that potential vaccines based on the cytotoxin may benefit from the use of the intact molecule.

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Selected References

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