Development of Hillchol®, a low-cost inactivated single strain Hikojima oral cholera vaccine

Cholera remains an important global health problem with up to 4 million cases and 140,000 deaths annually. Oral cholera vaccines (OCVs) are now a cornerstone of the WHOs "Ending Cholera - A Global Roadmap to 2030" global program for the eventual elimination of cholera. There are currently three WHO prequalified OCVs available, Dukoral (R), Shanchol (R) and Euvichol-Plus (R). These vaccines are effective but due to a multiple strain composition and two different methods of inactivation, are complex and costly to manufacture. We describe here the characterization and industrial scale development of Hillchol (R); a novel, likely affordable single-component OCV for low and middle-income countries. Hillchol (R) consists of formalin-inactivated bacteria of a stable recombinant Vibrio cholerae O1 El Tor Hikojima serotype strain expressing approximately 50% each of Ogawa and Inaba O1 LPS antigens. The novel OCV can be manufactured on an industrial scale at a low cost. Hillchol (R) was well tolerated in animal toxicology studies and shown to have non-inferior oral immunogenicity in mice for both intestinalmucosal and serological immune responses when compared with a WHO-prequalified OCV. The optimized production of this single component OCV will reduce cost of OCV production and thus substantially increase vaccine availability. Based on these results, Hillchol (R) has been produced at a GMP facility and used successfully for clinical phase I/II studies. (C) 2020 MSD Wellcome Trust Hilleman Laboratories Pvt Ltd. Published by Elsevier Ltd.