A randomized, placebo-controlled trial of the bivalent killed, whole-cell, oral cholera vaccine in adults and children in a cholera endemic area in Kolkata, India
Dilip Mahalanabis, Anna Lena Lopez, Dipika Sur, Jacqueline Deen, Byomkesh Manna, Suman Kanungo, Lorenz von Seidlein, Rodney Carbis, Seung Hyun Han, Seong Hye Shin, Stephen Attridge, Raman Rao, Jan Holmgren, John Clemens, Sujit K Bhattacharya, Dilip Mahalanabis, Anna Lena Lopez, Dipika Sur, Jacqueline Deen, Byomkesh Manna, Suman Kanungo, Lorenz von Seidlein, Rodney Carbis, Seung Hyun Han, Seong Hye Shin, Stephen Attridge, Raman Rao, Jan Holmgren, John Clemens, Sujit K Bhattacharya
Abstract
Objectives: An effective vaccine against cholera has been used for public health purposes in Vietnam since the 1990s. This vaccine was reformulated to meet WHO requirements. We assessed the safety and immunogenicity of the reformulated bivalent (Vibrio cholerae 01 and 0139) killed whole cell oral vaccine in a cholera endemic area in Kolkata, India.
Design: Double-blind, randomized, placebo controlled trial.
Setting: The trial was conducted in the clinical trial ward of the Infectious Diseases Hospital in Kolkata, India.
Participants: The participants were 101 healthy adults (males and non-pregnant females) aged 18-40 years and 100 healthy children (males and non-pregnant females) aged 1-17 years.
Interventions: Participants were randomized to receive either the bivalent killed whole cell oral cholera vaccine or placebo (killed oral Escherichia coli K12).
Outcome measures: For safety: proportion of subjects with adverse events during the duration of study participation. For immunogenicity: Proportion of subjects who had a > or = 4-fold rise in serum vibriocidal antibody titers 14 days after the second dose of vaccine or placebo.
Results: Adverse reactions were observed with similar frequency among vaccine and placebo recipients in both age groups. Among adults 4% of vaccine and 8% of placebo recipients and among children 4% of vaccine and 2% of placebo recipients had at least one adverse event within 28 days of the first dose of the vaccine. Following immunization, 53% of adult and 80% of children vaccinees showed a > or = 4 fold rise in serum V. cholerae O1 vibriocidal antibody titers. A less pronounced response to V. cholerae O139 vibriocidal antibody titers post-immunization was noted among vaccinees.
Conclusions: We found the vaccine to be safe and immunogenic in a cholera-endemic area in India.
Trial registration: ClinicalTrials.gov NCT00119197.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
Figures
References
- World Health Organization Global Task Force on Cholera Control. Cholera Vaccines: A new public health tool? 2002. Report of a WHO meeting, 10–11 December Geneva, Switzerland: World Health Organization.
- Trach DD, Clemens JD, Ke NT, Thuy HT, Son ND, et al. Field trial of a locally produced, killed, oral cholera vaccine in Vietnam. Lancet. 1997;349:231–235.
- Trach DD, Cam PD, Ke NT, Rao MR, Dinh D, et al. Investigations into the safety and immunogenicity of a killed oral cholera vaccine developed in Viet Nam. Bull World Health Organ. 2002;80:2–8.
- Thiem VD, Deen JL, von Seidlein L, Canh do G, Anh DD, et al. Long-term effectiveness against cholera of oral killed whole-cell vaccine produced in Vietnam. Vaccine. 2006;24:4297–4303.
- Vu DT, Hossain MM, Nguyen DS, Nguyen TH, Rao MR, et al. Coverage and costs of mass immunization of an oral cholera vaccine in Vietnam. J Health Popul Nutr. 2003;21:304–308.
- Anh DD, Canh do G, Lopez AL, Thiem VD, Long PT, et al. Safety and immunogenicity of a reformulated Vietnamese bivalent killed, whole-cell, oral cholera vaccine in adults. Vaccine. 2007;25:1149–1155.
- Clemens JD, Stanton BF, Chakraborty J, Sack DA, Khan MR, et al. B subunit-whole cell and whole cell-only oral vaccines against cholera: studies on reactogenicity and immunogenicity. J Infect Dis. 1987;155:79–85.
- Jertborn M, Svennerholm AM, Holmgren J. Saliva, breast milk, and serum antibody responses as indirect measures of intestinal immunity after oral cholera vaccination or natural disease. J Clin Microbiol. 1986;24:203–209.
- Attridge SR, Johansson C, Trach DD, Qadri F, Svennerholm AM. Sensitive microplate assay for detection of bactericidal antibodies to Vibrio cholerae O139. Clin Diagn Lab Immunol. 2002;9:383–387.
- Qadri F, Svennerholm AM, Shamsuzzaman S, Bhuiyan TR, Harris JB, et al. Reduction in capsular content and enhanced bacterial susceptibility to serum killing of Vibrio cholerae O139 associated with the 2002 cholera epidemic in Bangladesh. Infect Immun. 2005;73:6577–6583.
- Rao MR, Blackwelder WC, Troendle JF, Naficy AB, Clemens JD. Sample size determination for phase II studies of new vaccines. Vaccine. 2002;20:3364–3369.
- Gotuzzo E, Butron B, Seas C, Penny M, Ruiz R, et al. Safety, immunogenicity, and excretion pattern of single-dose live oral cholera vaccine CVD 103-HgR in Peruvian adults of high and low socioeconomic levels. Infect Immun. 1993;61:3994–3997.
- Taylor DN, Cardenas V, Perez J, Puga R, Svennerholm AM. Safety, immunogenicity, and lot stability of the whole cell/recombinant B subunit (WC/rCTB) cholera vaccine in Peruvian adults and children. Am J Trop Med Hyg. 1999;61:869–873.
- Losonsky GA, Lim Y, Motamedi P, Comstock LE, Johnson JA, et al. Vibriocidal antibody responses in North American volunteers exposed to wild-type or vaccine Vibrio cholerae O139: specificity and relevance to immunity. Clin Diagn Lab Immunol. 1997;4:264–269.
- Qadri F, Mohi G, Hossain J, Azim T, Khan AM, et al. Comparison of the vibriocidal antibody response in cholera due to Vibrio cholerae O139 Bengal with the response in cholera due to Vibrio cholerae O1. Clin Diagn Lab Immunol. 1995;2:685–688.
Source: PubMed