The current status of cholera vaccine development and experience with cholera vaccine trials in volunteers.

In recent years notable advances have been made in the development of improved vaccines to prevent cholera. These new vaccines are administered orally to maximally stimulate intestinal secretory immunity. Killed vibrios, given in conjunction with purified B subunit or administered alone, in three spaced doses, caused no adverse reactions and have conferred significant protection in volunteer challenge studies and in field trials. Two attenuated mutants of V. cholerae, prepared by recombinant DNA techniques, CVD 103 and CVD 103-HgR are well-tolerated and elicit prominent immune responses and protective immunity after ingestion of a single oral dose. Other modern approaches being pursued include the development of auxotrophic strains and of modifying attenuated S. typhi strain Ty21a to express V. cholerae Inaba and Ogawa LPS antigens.

The current status of typhoid vaccine development and clinical trials with typhoid vaccines.

The killed whole cell typhoid vaccines, although protective, have limited usefulness because of the adverse reactions they evoke. In contrast, new typhoid vaccines protect without reactogenicity. Attenuated oral vaccine Ty2la has been evaluated in field trials of efficacy in Santiago, Chile. Three doses of Ty2la in an enteric-coated formulation given within one week provided 69% efficacy for at least four years. Ty2la has reached the stage of being a practical public health tool. Two double auxotrophic (Aro-, Pur-) mutant strains of S. typhi (541Ty and 543Ty) were well-tolerated and stimulated cell-mediated immune responses but evoked little serological response. Parenteral purified Vi polysaccharide of S. typhi (single 25 mcg dose) was safe and immunogenic and provided 64-72% protection (for at least 17-21 months) in controlled field trials in Nepal and South Africa.