Development of Peru-15 (CholeraGarde), a live-attenuated oral cholera vaccine: 1991-2009.

Epidemics of severe dehydrating cholera are on the increase in resource-limited settings around the world. Adults, children and young infants are all at risk of these infections. Considerable efforts have been made for the development of safe and efficacious oral cholera vaccines over the last three decades. Whole-cell-inactivated as well as live oral cholera vaccines have been developed and tested in different field settings to determine the efficacy and/or effectiveness of such vaccines for reducing life-threatening disease. This review follows the trail of the development of CholeraGarde, a live-attenuated Vibrio cholerae O1 vaccine candidate of the El Tor biotype and Inaba serotype. CholeraGarde, also well known as Peru-15, was derived from V. cholerae O1 strain C6709, a clinical isolate from Peru. The vaccine has now been tested in over 500 individuals, adults and children and shows a good safety and immunogenicity profile. At a dose of around 10(8) CFU, it is immunogenic in adults in the USA, as well as in adults, children and infants in Bangladesh. The vaccine has been tested in infants of 9 months of age where a single 10(8) CFU dose was safe and immunogenic while a tenfold lower dose was not. Excretion of the strain was higher in adults in the USA and low in Bangladeshi participants in all age groups. Phase II studies of CholeraGarde are ongoing in cholera-endemic countries to concomitantly administer it to infants with the parenteral measles vaccine. Studies on HIV-positive individuals are also ongoing to determine safety, immunogenicity and contraindications, if any. Phase III studies are being targeted to determine the protective efficacy of CholeraGarde and for further development of a single-dose vaccine that will protect infants and also other age groups from endemic and epidemic cholera.