The oral cholera vaccine Shanchol™ when stored at elevated temperatures maintains the safety and immunogenicity profile in Bangladeshi participants

Tuesday, 15th of March 2016

Vaccine, Volume 34, Issue 13, 18 March 2016, Pages 1551–1558

The oral cholera vaccine Shanchol™ when stored at elevated temperatures maintains the safety and immunogenicity profile in Bangladeshi participants

Amit Saha ^a^,^b,
Arifuzzaman Khan ^a,
Umme Salma ^a,
Nusrat Jahan ^a,
Taufiqur Rahman Bhuiyan ^a,
Fahima Chowdhury ^a,
Ashraful Islam Khan ^a,
Farhana Khanam ^a,
Sundaram Muruganandham ^e,
Sreeramulu Reddy Kandukuri ^e,
Mandeep Singh Dhingra ^e,
John D. Clemens ^a^,^d,
Alejandro Cravioto ^c,
Firdausi Qadri ^a^, ,
^a International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b), Dhaka, Bangladesh
^b University of New South Wales, SPHCM, NSW, Australia
^c Global Evaluative Sciences USA, Inc., Seattle, WA 98109, United States
^d UCLA Fielding School of Public Health, Los Angeles, United States
^e Shantha Biotechnics Private Limited, Hyderabad, India

Received 20 December 2015, Revised 3 February 2016, Accepted 4 February 2016, Available online 16 February 2016

Highlights

• The OCV, Shanchol remains stable and is safe in humans after storage at 42 °C.

• The vaccine is immunogenic in humans after storage at elevated temperatures.

• These findings will help change regulations requiring cold chain for such OCVs.

Abstract

Background

The oral cholera vaccine (OCV), Shanchol™ has shown protective efficacy lasting up to 5 years, however, requirement for a cold chain limits its use in resource poor settings. The study was conducted to determine the safety and immunogenicity of Shanchol in adult participants in Bangladesh when stored at elevated temperatures.

Methods

The study was conducted in Mirpur, Dhaka. Four groups of healthy adult participants received two doses of Shanchol™, kept under standard storage temperature (Group A; 2–8 °C) or at elevated temperatures (Group B, 25 °C; Group C, 37 °C; Group D, 42 °C) for 14 days, respectively. Vaccine specific antibody responses were determined.

Findings

145 participants were assigned to each group. Adverse events were mild not differing among groups. Vaccine stored at elevated temperatures remained stable with cumulative LPS content within admissible limits.

Vibriocidal antibody responses were observed in all groups after each dose of vaccine at day 7 and 21 compared to pre-immune levels (P < 0.001). Four-fold increases to Vibrio cholerae O1 Ogawa were observed at day 7 and/or day 21 after vaccination in the standard temperature and the three elevated temperature groups, with responder rates of; 76% (95% CI LB; 70%), 80% (95% CI LB; 74%), 69% (95% CI LB; 63%), and 74% (95% CI LB; 68%) in Groups A–D, respectively (P = 0.240). Responses were also seen in all groups to V. cholerae O1 Inaba and V. cholerae O139 and in LPS specific IgA response to V. cholerae O1 antigens.

Interpretation

This is the first report to show that the OCV is stable at elevated temperatures, and the safety and immunogenicity profiles are not altered. This information will help formulate global policies for use of the vaccine at higher temperatures, resulting in easier distribution and vaccination costs and decrease logistical challenges to vaccine delivery.

Funding

Bill & Melinda Gates Foundation.

Trial registration

Clinical Trials.gov number NCT01762930.