Therapeutic Equivalence, Immunogenicity, and Safety of Euvichol Oral Cholera Vaccine Formulations Compared with WHO-prequalified Shanchol vaccine in Healthy Children and Adults: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Abstract

Preprint Description Background: Global demand for oral cholera vaccines (OCVs) has increased substantially, while the discontinuation of Shanchol has increased reliance on Euvichol-based formulations. This systematic review and meta-analysis evaluated the immunogenicity and safety of Euvichol vaccine formulations compared with Shanchol. Methods: We systematically reviewed randomized controlled trials comparing Euvichol, Euvichol-Plus, Euvichol-S, or Cholvax with Shanchol in healthy children and adults. Primary immunogenicity outcomes were vibriocidal seroconversion rates against Vibrio cholerae O1 Inaba and O1 Ogawa following the two-dose vaccination schedule. Safety outcomes included solicited and unsolicited adverse events and serious adverse events. Meta-analyses were conducted using risk ratios and other appropriate effect measures according to outcome characteristics. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and certainty of evidence was evaluated using GRADE. Results: Five randomized controlled trials were included. Across the principal immunogenicity analyses, Euvichol formulations demonstrated comparable vibriocidal seroconversion responses to Shanchol for both O1 Inaba and O1 Ogawa, with low statistical heterogeneity. Safety outcomes were also broadly comparable between vaccine groups, and serious adverse events were rare. Conclusions: The available randomized evidence supports comparable short-term immunogenicity and safety of Euvichol-based oral cholera vaccine formulations relative to Shanchol. These findings support the continued evaluation and use of Euvichol-based formulations within global oral cholera vaccine supply and outbreak-response strategies, while recognizing the limited number of trials, reliance on immunogenicity surrogate endpoints, and limited long-term effectiveness data. Study type: Systematic review and meta-analysis of randomized controlled trials. Keywords: cholera; oral cholera vaccine; Euvichol; Euvichol-Plus; Euvichol-S; Cholvax; Shanchol; immunogenicity; seroconversion; vaccine safety; systematic review; meta-analysis.