Effect of Extended Dose Intervals on the Immune Response to Oral Cholera Vaccine

Summary

Cholera is a life-threatening disease if prompt actions are not taken. The most recent estimates of the global burden of cholera estimate that there are more than 1.3 billion people at risk. Of which, 2.86 million (range: 1.3-4.0 million) will contract cholera and 95,000 (21,000-143,000) will die each year. A safe, effective, and affordable killed whole-cell oral cholera vaccine (OCV) is now being used widely to prevent cholera in areas at risk. This regimen demonstrated 65% efficacy retained for at least 3 years and even up to 5 years in an endemic setting. The primary aim of this project is to determine changes in the vibriocidal geometric mean titers (GMT) in subjects who receive the second dose of oral cholera vaccine (OCV) at different intervals: 2 weeks, or 6 months following the first dose of vaccine. Secondary aims include a) vibriocidal antibody response rates in subjects who receive OCV at 2 weeks or 6 months following the first dose of vaccine, b) age specific serum vibriocidal GMTs following the second dose among participants given the second dose of OCV at intervals of 2 weeks or 6 months following the first dose of vaccine, c) GMT and antibody response rates of Immunoglobulin A (IgA) and Immunoglobulin G (IgG) anti-lipopolysaccharide (anti-LPS) as measured by ELISA following the second dose among participants given the second dose of OCV at intervals of 2 weeks or 6 months following the first dose of vaccine. Our hypothesis is that the vibriocidal GMT following the second dose, when given after 6 months will not be inferior to the response when the second dose is given according to the standard interval of two weeks.

Timeline

Start

2017-11-16

Primary completion

2019-10-16

Completion

2020-12-01

Publications

• Background Ali M, Nelson AR, Lopez AL, Sack DA. Updated global burden of cholera in endemic countries. PLoS Negl Trop Dis. 2015 Jun 4;9(6):e0003832. doi: 10.1371/journal.pntd.0003832. eCollection 2015.
• Background Sridhar S. An affordable cholera vaccine: an important step forward. Lancet. 2009 Nov 14;374(9702):1658-60. doi: 10.1016/S0140-6736(09)61418-5. Epub 2009 Oct 8. No abstract available.
• Background Bi Q, Ferreras E, Pezzoli L, Legros D, Ivers LC, Date K, Qadri F, Digilio L, Sack DA, Ali M, Lessler J, Luquero FJ, Azman AS; Oral Cholera Vaccine Working Group of The Global Task Force on Cholera Control. Protection against cholera from killed whole-cell oral cholera vaccines: a systematic review and meta-analysis. Lancet Infect Dis. 2017 Oct;17(10):1080-1088. doi: 10.1016/S1473-3099(17)30359-6. Epub 2017 Jul 17.
• Background Bhattacharya SK, Sur D, Ali M, Kanungo S, You YA, Manna B, Sah B, Niyogi SK, Park JK, Sarkar B, Puri MK, Kim DR, Deen JL, Holmgren J, Carbis R, Dhingra MS, Donner A, Nair GB, Lopez AL, Wierzba TF, Clemens JD. 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 Dec;13(12):1050-6. doi: 10.1016/S1473-3099(13)70273-1. Epub 2013 Oct 18.
• Background Kanungo S, Desai SN, Nandy RK, Bhattacharya MK, Kim DR, Sinha A, Mahapatra T, Yang JS, Lopez AL, Manna B, Bannerjee B, Ali M, Dhingra MS, Chandra AM, Clemens JD, Sur D, Wierzba TF. Flexibility of oral cholera vaccine dosing-a randomized controlled trial measuring immune responses following alternative vaccination schedules in a cholera hyper-endemic zone. PLoS Negl Trop Dis. 2015 Mar 12;9(3):e0003574. doi: 10.1371/journal.pntd.0003574. eCollection 2015 Mar.
• Mwaba J, Chisenga CC, Xiao S, Ng'ombe H, Banda E, Shea P, Mabula-Bwalya C, Mwila-Kazimbaya K, Laban NM, Alabi P, Chirwa-Chobe M, Simuyandi M, Harris J, Iyer AS, Bosomprah S, Scalzo P, Murt KN, Ram M, Kwenda G, Ali M, Sack DA, Chilengi R, Debes AK. Serum vibriocidal responses when second doses of oral cholera vaccine are delayed 6 months in Zambia. Vaccine. 2021 Jul 22;39(32):4516-4523. doi: 10.1016/j.vaccine.2021.06.034. Epub 2021 Jul 1.

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