Nontoxigenic Vibrio cholerae Challenge Strains for Evaluating Vaccine Efficacy and Inferring Mechanisms of Protection
Bolutife Fakoya, Karthik Hullahalli, Daniel H. F. Rubin, Deborah R. Leitner, Roma Chilengi, David A. Sack, Matthew K. Waldor
Abstract
Human challenge studies are a valuable method for testing the efficacy of cholera vaccines. However, challenge studies cannot be performed in countries of cholera endemicity due to safety concerns; also, contemporary pandemic Vibrio cholerae strains are not used in current challenge studies. To facilitate cholera research, we derived nontoxigenic challenge strains of both V. cholerae serotypes from a 2016 clinical isolate from Zambia and demonstrated how they can be used to gauge cholera immunity accurately and safely. These strains were also genetically barcoded, adding the potential for analyses of V. cholerae population dynamics to challenge studies. Preclinical analyses presented here suggest that these strains have the potential to enhance the safety, relevance, and scope of future cholera vaccine challenge studies and be valuable reagents for studies of immunity to cholera.