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.
Publication types
-
Clinical Trial
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Administration, Oral
-
Adolescent
-
Adult
-
Antibody Formation
-
Child
-
Cholera / immunology*
-
Cholera / microbiology
-
Cholera / pathology
-
Cholera / prevention & control
-
Cholera Vaccines / administration & dosage*
-
Cholera Vaccines / adverse effects
-
Cholera Vaccines / immunology
-
Female
-
Headache / epidemiology
-
Headache / immunology
-
Headache / pathology
-
Humans
-
Immunogenicity, Vaccine*
-
India / epidemiology
-
Male
-
Vaccination / methods
-
Vaccines, Inactivated / administration & dosage
-
Vaccines, Inactivated / adverse effects
-
Vaccines, Inactivated / immunology
-
Vibrio cholerae O1 / immunology
-
Vibrio cholerae O1 / pathogenicity
-
Vibrio cholerae O139 / immunology
-
Vibrio cholerae O139 / pathogenicity
-
Young Adult
Substances
-
Cholera Vaccines
-
Vaccines, Inactivated
Associated data
-
ClinicalTrials.gov/NCT00760825
-
CTRI/CTRI/2012/01/002354
Grants and funding
This study was funded by the Bill and Melinda Gates Foundation through a grant to the International Vaccine Institute, Seoul. Venkata Raghava Mohan and Santosh Raj were study investigators who received funds to their institutes from the International Vaccine Institute to support their work in this study and did not directly receive any funds. The investigators’ institution had no additional role in the study or in preparation of the manuscript and the decision to publish. Ajit Pal Singh, Deok Ryun Kim, Yanghee Kim and Binod Sah were employed by the International Vaccine Institute at the time of the study and were involved in the study design, implementation and supervision of the study, managed data collection and statistical analyses. The International Vaccine Institute had the opportunity to review the manuscript but did not have any role in the preparation of the manuscript or in the decision to publish. The vaccine was provided by Shantha Biotechnics Pvt. Ltd (a Sanofi Company), Hyderabad, India. Mandeep Singh Dhingra, Naveena Aloysia D’Cor, Tarun Saluja, Venkat Jayanth Midde, Sridhar Vemula and Santhosh Kumar Narla were employees of Shantha Biotechnics Pvt Ltd at the time of the study and participated in one or all of the following: the trial design, monitored data collection and managed the writing of the report. Mandeep Singh Dhingra is currently employed by Sanofi Pasteur, USA (part of the parent company of Shantha Biotechnics Pvt. Ltd). Shantha Biotechnics Pvt had the opportunity to review the manuscript but were not involved in decision to publish. Funding for assistance with preparation of the manuscript was provided by Sanofi Pasteur. The specific roles of these authors are articulated in the ‘author contributions’ section.