Safety and immunogenicity of a killed bivalent (O1 and O139) whole-cell oral cholera vaccine in adults and children in Vellore, South India

Abstract

This open-label study assessed the safety and immunogenicity of two doses (14 days apart) of an indigenously manufactured, killed, bivalent (Vibrio cholerae O1 and O139), whole-cell oral cholera vaccine (SHANCHOL; Shantha Biotechnics) in healthy adults (n = 100) and children (n = 100) in a cholera endemic area (Vellore, South India) to fulfill post-licensure regulatory requirements and post-World Health Organization (WHO) prequalification commitments. Safety and reactogenicity were assessed, and seroconversion rates (i.e. proportion of participants with a ≥ 4-fold rise from baseline in serum vibriocidal antibody titers against V. cholerae O1 Inaba, O1 Ogawa and O139, respectively) were determined 14 days after each vaccine dose. No serious adverse events were reported during the study. Commonly reported solicited adverse events were headache and general ill feeling. Seroconversion rates after the first and second dose in adults were 67.7% and 55.2%, respectively, against O1 Inaba; 47.9% and 45.8% against O1 Ogawa; and 19.8% and 20.8% against O139. In children, seroconversion rates after the first and second dose were 80.2% and 68.8%, respectively, against O1 Inaba; 72.9% and 67.7% against O1 Ogawa; and 26.0% and 18.8% against O139. The geometric mean titers against O1 Inaba, O1 Ogawa, and O139 in both adults and children were significantly higher after each vaccine dose compared to baseline titers (P < 0.001; for both age groups after each dose versus baseline). The seroconversion rates for O1 Inaba, O1 Ogawa, and O139 in both age groups were similar to those in previous studies with the vaccine. In conclusion, the killed, bivalent, whole-cell oral cholera vaccine has a good safety and reactogenicity profile, and is immunogenic in healthy adults and children. Trial Registration: ClinicalTrials.gov NCT00760825; CTRI/2012/01/002354.

Conflict of interest statement

Venkata Raghava Mohan, Santosh Raj, Ajit Pal Singh, Deok Ryun Kim, Yanghee Kim, Binod Sah and Mohammad Ali have no relevant conflict of interest to declare. Naveena Aloysia D’Cor, Venkat Jayanth Midde, Sridhar Vemula and Santhosh Kumar Narla are employed by Shantha Biotechnics Pvt. Ltd, a Sanofi Company. Tarun Saluja was employed by Shantha Biotechnics Pvt. Ltd at the time of study but is currently an employee of the International Vaccine Institute, Seoul. Mandeep Singh Dhingra was an employee of Shantha Biotechnics Pvt. Ltd at the time of the study but is currently an employee of Sanofi Pasteur, USA (part of the parent company of Shantha Biotechnics Pvt. Ltd). Mandeep Singh Dhingra and Naveena Aloysia D’Cor also own stock interests in Sanofi. The International Vaccine Institute, Seoul received funding from the Bill and Melinda Gates Foundation to study the oral cholera vaccine (Shanchol), but has no commercial interest in the vaccine. The vaccine was provided by Shantha Biotechnics Pvt. Ltd (a Sanofi Company). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Summary of the flow of participants through the study.

Fig 2. Percentage seroconversion for V. cholera O1 Inaba, V. cholera O1 Ogawa and V. cholera O139 in adults and children after one and two doses of whole-cell OCV.

Fig 3. Percentage seroconversion for V. cholera O1 Inaba, V. cholera O1 Ogawa and V. cholera O139 in children aged 1–4 years and 5–17 years after receiving one and two doses of whole-cell OCV.

Fig 4. GMT for V. cholera O1 Inaba, and V. cholera O1 Ogawa in children aged 1–4 years and 5–17 years after one and two doses of whole-cell OCV.

Fig 5. GMT for V. cholera O139 in children aged 1–4 years and 5–17 years after one and two doses of whole-cell OCV.

Fig 6. Geometric mean-fold rise in titers to V. cholerae O1 Inaba, V. cholerae O1 Ogawa and V. cholerae O139 between baseline and 14 days after the first dose of vaccine, and baseline and 14 days after the second dose of vaccine.

Fig 7. Comparison of seroconversion rates with the whole-cell OCV in studies conducted in cholera endemic areas [5, 6, 10].