A Randomized, Placebo-Controlled Trial Evaluating Safety and Immunogenicity of the Killed, Bivalent, Whole-Cell Oral Cholera Vaccine in Ethiopia

Abstract

Killed whole-cell oral cholera vaccine (OCV) has been a key component of a comprehensive package including water and sanitation measures for recent cholera epidemics. The vaccine, given in a two-dose regimen, has been evaluated in a large number of human volunteers in India, Vietnam, and Bangladesh, where it has demonstrated safety, immunogenicity, and clinical efficacy. We conducted a double-blind randomized placebo-controlled trial in Ethiopia, where we evaluated the safety and immunogenicity of the vaccine in 216 healthy adults and children. OCV was found to be safe and elicited a robust immunological response against Vibrio cholerae O1, with 81% adults and 77% children demonstrating seroconversion 14 days after the second dose of vaccine. This is the first study to evaluate safety and immunogenicity of the vaccine in a population outside Asia using a placebo-controlled, double-blind, randomized study design.

Comparison of immune responses to a killed bivalent whole cell oral cholera vaccine between endemic and less endemic settings

“…No adverse events or serious adverse events occurred more frequently among vaccinees compared to placebo recipients in either population . The vaccine was shown to be immunogenic in both the Ethiopian and Indian cohorts.…”

“…Details on study agents, sites, procedures and assembly of participants in these individually randomised, double blind, placebo‐controlled trials have been reported previously . In both trials, healthy adults (18 years and above) and children (1–17 years) were recruited.…”

Immunogenicity of a killed bivalent whole cell oral cholera vaccine in forcibly displaced Myanmar nationals in Cox's Bazar, Bangladesh

“…The baseline vibriocidal titers in the different age groups of vaccinees among the FDMN population were similar when compared to the responses seen in Bangladeshi healthy participants who had received Shanchol in another study (NCT02823899). When compared with results with the results of the FDMNs with other non endemic countries like Ethiopia and Haiti, it is seen that FDMN population had higher baseline vibriocidal geometric mean titer (GMT) to Ogawa (24 vs. 14 vs. 72) as well as Inaba (16 vs.11 vs. 44) serotypes seen in Ethiopia, Haiti and FDMN respectively [24,25]. This result also suggests that the FDMN population were already exposed to Vibrio cholerae O1.…”

Achievements and challenges for the use of killed oral cholera vaccines in the global stockpile era

“…33 Interestingly, this may be directly related to the amount of natural exposure and pre-existing antibodies since higher seroconversion rates were noted following a second dose in comparatively less endemic areas in Haiti and Ethiopia. 29,34,35 This suggests that there may be important geographical differences in immunological response in areas of varying cholera exposure. A phase 3 placebo RCT assessing a single dose of Shanchol in over 200,000 individuals from the hyperendemic setting of Bangladesh found an efficacy of 40% against all cholera cases and 60% protective against cholera cases with severe dehydration over a 6 month period.…”

“…[27][28][29] Shanchol has conferred 67% protection in a double blind randomized placebo controlled trial in more than 67,000 children and adults in Kolkata, India. 30 However, levels of protection were not uniform across all age groups.…”