Table 1.

Timeline of major milestones in the development of Cholera vaccines.

1894–1960 •Development of several injectable whole-cell cholera vaccines

1980s •Monovalent killed whole-cell oral cholera vaccine developed at University of Gothenburg, Sweden •Technology transfer from University of Gothenburg to Vietnam and production of oral cholera vaccine in Vietnam

1991 •Licensure of monovalent killed whole-cell oral cholera vaccine developed at University of Gothenburg (Dukoral®); Dukoral mainly marketed as travelers’ vaccine

1997 •Reformulation and production of the Vietnamese vaccine by VaBiotech. The vaccine is licensed as ORC-Vax™ in Vietnam

Early 2000s •Initiation of partnership between IVI and VaBiotech •Reformulation of the VaBiotech vaccine in collaboration with IVI

2001 •WHO prequalification of Dukoral®

2002–2005 •Clinical trials of the IVI-reformulated vaccine in Vietnam and India demonstrate vaccine is safe and immunogenic •Initiation of partnership between IVI and Shantha Biotechnics Ltd., in India •Technology transfer from VaBiotech to Shantha Biotechnics Ltd

2006 •Cluster-randomized, placebo-controlled efficacy trial with IVI-reformulated vaccine in Kolkata, India demonstrate that the vaccine is safe and efficacious (65%)

2009 •Licensure of IVI-reformulated vaccine in Vietnam (mORCVAX™) •Licensure of IVI-reformulated vaccine in India (Shanchol®)

2010 •WHO Position Paper recommends OCV to be used in endemic areas and to be considered for use in areas at risk for outbreaks •Initiation of partnership between IVI and EuBiologics in South Korea •Laboratory-scale technology transfer (3L) from IVI to EuBiologics

2011 •WHO prequalification of Shanchol™ making it the first low-cost OCV available for the global market •EuBiologics produce Euvichol® in 100L fermenter •Pre-clinical studies of Euvichol

2012 •Phase I clinical study of Euvichol® in Korea

2013 •A global cholera vaccine stockpile is created •Gavi supports stockpile

2014 •WHO recommendation of OCV in humanitarian emergencies •Clinical studies of Euvichol® in the Philippines demonstrate vaccine is safe and efficacious •Financing for Euvichol® development and production scale-up to EuBiologics by investors •Production capacity scale-up (100L to 600L fermenter) by EuBiologics increases Euvichol® production to up to 25 million doses per year

2015 •OCV demand surpasses global supply •WHO prequalification of Euvichol®

2016 •WHO prequalification of 600L scale (No thimerosal) Euvichol variation •Long term arrangement with UNICEF signed for Euvichol

2017 •WHO prequalification of Euvichol-Plus®