Development of improved cholera vaccine based on subunit toxoid.

Abstract

THE cholera vaccines now available consist of killed vibrios, and give rise to only limited protection of short duration1. The finding that the excessive diarrhoea in cholera is due to the action on the small intestine epithelium of an exotoxin produced by the vibrios2,3 has focused attention on the potential of toxoid for improved immunoprophylaxis. The development of a suitable toxoid has met with great difficulties, however. Formalin toxoid, although reasonably antigenic, proved unsatisfactory because of reversion to toxicity4. Glutaraldehyde toxoid was stable but poorly immunogenic which explains its low efficacy in a recent field trial5. We describe here the development and properties of a subunit cholera toxoid, the nature of which eliminates the risk of reversion to toxicity. The high protective immunogenicity observed in experimental animals gives promise that addition of this toxoid to the conventional vaccine will result in a significantly improved immunoprophylactic agent against cholera.