CHOLERA VACCINE - DEVELOPMENTAL STRATEGIES AND PROBLEMS

Over a hundred years have elapsed since Vibrio cholerae, the etiologic al agent for the disease cholera, was discovered by Robert Kockh. Ever since then serious efforts have been made to develop prophylactic mea sures to combat the disease without much success. Seven pandemics have so far been reported and cholera still remains a public health proble m in developing countries. Several strategies have been adopted to dev elop; vaccines against the disease and many of these vaccines have und ergone field trials. During the last two decades, an enormous amount o f information has accumulated regarding the organism V. cholerae, its virulence factors, including cholera toxin, and the molecular basis of its pathogenicity. In recent years, with the advent of recombinant DN A technology and major breakthroughs in molecular biology and immunolo gy a new dimension has been given to the design of vaccine strains. Th e second: generation live oral vaccines will perhaps soon replace the long-used first generation parenterally administered killed whole cell vaccines which offered protection for not more than three months. All the recombinant vaccines tested so far produced adverse reactions in volunteers, although they provided varying degrees of protection upto about one year of surveillance. Parallel to the trials of live oral va ccines, combination vaccines comprising killed whole cells and purifie d B subunit of cholera toxin was also tried. These vaccines had minima l side-effects but the efficacy was not upto expectations. From the fa ilure of each vaccine strain, new information had emerged and improved strategies were adopted. This led to the discovery of new toxins in V . cholera other than the cholera toxin, which were held responsible fo r the adverse effects observed for vaccine strains attenuated only in the cholera toxin genes. Recently nontoxinogenic clinical isolates hav e been used to construct vaccine strains. This strategy should elimina te any adverse effects that might originate due to the presence of mul tiple toxins. In spite of all efforts made all over the world, there i s yet no safe and efficacious vaccine for cholera. This article review s the strategies employed so far in this quest and the problems encoun tered in developing a truly effective vaccine.