Flexibility of oral cholera vaccine dosing-a randomized controlled trial measuring immune responses following alternative vaccination schedules in a cholera hyper-endemic zone
Suman Kanungo, Sachin N Desai, Ranjan Kumar Nandy, Mihir Kumar Bhattacharya, Deok Ryun Kim, Anuradha Sinha, Tanmay Mahapatra, Jae Seung Yang, Anna Lena Lopez, Byomkesh Manna, Barnali Bannerjee, Mohammad Ali, Mandeep Singh Dhingra, Ananga Mohan Chandra, John D Clemens, Dipika Sur, Thomas F Wierzba, Suman Kanungo, Sachin N Desai, Ranjan Kumar Nandy, Mihir Kumar Bhattacharya, Deok Ryun Kim, Anuradha Sinha, Tanmay Mahapatra, Jae Seung Yang, Anna Lena Lopez, Byomkesh Manna, Barnali Bannerjee, Mohammad Ali, Mandeep Singh Dhingra, Ananga Mohan Chandra, John D Clemens, Dipika Sur, Thomas F Wierzba
Abstract
Background: A bivalent killed whole cell oral cholera vaccine has been found to be safe and efficacious for five years in the cholera endemic setting of Kolkata, India, when given in a two dose schedule, two weeks apart. A randomized controlled trial revealed that the immune response was not significantly increased following the second dose compared to that after the first dose. We aimed to evaluate the impact of an extended four week dosing schedule on vibriocidal response.
Methodology/principal findings: In this double blind randomized controlled non-inferiority trial, 356 Indian, non-pregnant residents aged 1 year or older were randomized to receive two doses of oral cholera vaccine at 14 and 28 day intervals. We compared vibriocidal immune responses between these schedules. Among adults, no significant differences were noted when comparing the rates of seroconversion for V. cholerae O1 Inaba following two dose regimens administered at a 14 day interval (55%) vs the 28 day interval (58%). Similarly, no differences in seroconversion were demonstrated in children comparing the 14 (80%) and 28 day intervals (77%). Following 14 and 28 day dosing intervals, vibriocidal response rates against V. cholerae O1 Ogawa were 45% and 49% in adults and 73% and 72% in children respectively. Responses were lower for V. cholerae O139, but similar between dosing schedules for adults (20%, 20%) and children (28%, 20%).
Conclusions/significance: Comparable immune responses and safety profiles between the two dosing schedules support the option for increased flexibility of current OCV dosing. Further operational research using a longer dosing regimen will provide answers to improve implementation and delivery of cholera vaccination in endemic and epidemic outbreak scenarios.
Conflict of interest statement
MSD is an employee of Shantha Biotechnics. All other authors declare they have no conflicts of interest. This does not alter our adherence to all PLOS policies on sharing data and materials.
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References
- World Health Organization, Cholera 2012. Weekly epidemiological record, 2013. 88: p. 321–334.
- World Health Organization. Cholera Annual Report 2013. Weekly Epidemiological Record, 2014. 89(31): p. 345–356.
- Holmgren J. and Kaper J., Oral cholera vaccines 4th ed. New Generation Vaccines, ed. Levine M. 2009, New York: Marcel Deker.
- Anh D.D., et al., Safety and immunogenicity of a reformulated Vietnamese bivalent killed, whole-cell, oral cholera vaccine in adults. Vaccine, 2007. 25(6): p. 1149–55.
- Mahalanabis D., et al., 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. PLoS ONE [Electronic Resource], 2008. 3(6): p. e2323 10.1371/journal.pone.0002323
- Saha A., et al., Safety and immunogenicity study of a killed bivalent (O1 and O139) whole-cell oral cholera vaccine Shanchol, in Bangladeshi adults and children as young as 1 year of age. Vaccine, 2011. 29(46): p. 8285–8292. 10.1016/j.vaccine.2011.08.108
- Background Paper on the integration of Oral Cholera Vaccines into Global Cholera Programmes. 2009. World Health Organization Strategic Advisory Group of Experts (SAGE) on Immunization.
- Bhattacharya S.K., et al., 5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: a cluster-randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2013. October 17 pii: S1473–3099(13)70273–1. 10.1016/S1473-3099(13)70273-1
- Clemens J.D., et al., Field trial of oral cholera vaccines in Bangladesh. Lancet, 1986. 2(8499): p. 124–7.
- Clemens J.D., et al., Field trial of oral cholera vaccines in Bangladesh: results from three-year follow-up. Lancet, 1990. 335(8684): p. 270–3.
- van Loon F.P., et al., Field trial of inactivated oral cholera vaccines in Bangladesh: results from 5 years of follow-up. Vaccine, 1996. 14(2): p. 162–6.
- Kanungo S., et al., Immune responses following one and two doses of the reformulated, bivalent, killed, whole-cell, oral cholera vaccine among adults and children in Kolkata, India: a randomized, placebo-controlled trial. Vaccine, 2009. 27(49): p. 6887–6893. 10.1016/j.vaccine.2009.09.008
- Yang J.S., et al., A semi-automated vibriocidal assay for improved measurement of cholera vaccine-induced immune responses. J Microbiol Methods, 2007. 71(2): p. 141–6.
- Hintze, J. PASS 2008 NCSS Statistical Software LLC January 7, 2012]; Available from: .
- Newcombe R.G., Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med. 1998. April 30;17(8):857–72.
- Sur D., et al., The burden of cholera in the slums of Kolkata, India: data from a prospective, community based study. Archives of Disease in Childhood, 2005. 90(11): p. 1175–1181.
- Ali M., et al., Herd Protection by a Bivalent Killed Whole-Cell Oral Cholera Vaccine in the Slums of Kolkata, India. Clinical Infectious Diseases, 2013. 56(8): p. 1123–1131. 10.1093/cid/cit009
- Clemens J.D., et al., B subunit-whole cell and whole cell-only oral vaccines against cholera: studies on reactogenicity and immunogenicity. Journal of Infectious Diseases, 1987. 155(1): p. 79–85.
- Single Dose Oral Cholera Vaccine Study in Dhaka, Bangladesh (SCVB) NCT02027207 2014 June 24, 2014]; Available from: = single+dose%2C+cholera&rank = 1.
Source: PubMed