A Randomized Observer Blinded Controlled Non Inferiority Trial to Evaluate the Safety and Immunogenicity of Locally Manufactured Inactivated Bivalent Whole Cell-oral Cholera Vaccine (WC-OCV) 'Cholvax' in Bangladeshi Healthy Adults and Children

Background : Cholera continues to be a major cause of morbidity and mortality in low-income countries including Bangladesh. It is estimated that there are at least 300,000 severe cases and over 4,500 deaths in Bangladesh each year1. The overall morbidity for cholera remains high. A global stockpile of OCV has been created by WHO in 2013 for epidemic and outbreak settings2. However, the global demand for the vaccine far exceeds the present supply for both epidemic and also endemic settings3. It can be envisioned that local production of an affordable OCV for high risk population in endemic settings will improve the present scenario in Bangladesh and other countries.

Knowledge gap: The WHO recommends OCV for use in both endemic and epidemic cholera settings4. At present there are two vaccines that are WHO prequalified. These include Dukoral which is registered in Bangladesh and in over 50 countries. However, the disadvantage of use of Dukoral is that its current price it is expensive for Bangladesh and other developing countries. In addition, the need for buffer to formulate the vaccine makes it less fieldable for mass vaccination programs. Another whole cell killed OCV, ShancholTM, which is WHO prequalified, is based on similar bacterial components as Dukoral and licensed in India but not in Bangladesh. Although this vaccine is relatively affordable it may not be sufficiently cost effective for the Government of Bangladesh to implement it in our poor endemic settings. At present, the vaccine is in short supply and will not be able to meet the global demands. In order to increase supply of OCV and make the vaccine more affordable, a locally manufactured killed bivalent whole cell-oral cholera vaccine Cholvax is now available. The present study will evaluate the safety and immunogenicity of Cholvax as a test vaccine using Shanchol TM as the comparator vaccine in a non inferiority trial design.

Relevance: The study of this locally manufactured OCV, Cholvax among children and adults will be able to give us information regarding the safety and immunogenicity of the vaccine. Based on this information, it can be anticipated that regulatory requirements as well as licensure of the vaccine will be initiated in Bangladesh. This will pave the way forward for the future approval by WHO and for its global use. The introduction of Cholvax in endemic settings, seasonal outbreak as well as in the EPI program of the country in the future can be expected based on the study results; initiatives and plans can be made to introduce this locally produced vaccine in Bangladesh at an affordable cost and in the future globally.

Hypothesis (if any): Locally produced orally administered whole cell inactivated bivalent cholera vaccine, Cholvax is non inferior or at least as safe and immunogenic in adults and children in Bangladesh as compared to Shanchol TM.

Objectives: The objectives of this study are- i. To evaluate and compare the safety and immunogenicity of the Cholvax with ShancholTM ii. To evaluate the safety and immunogenicity of Cholvax in healthy adults and children in Dhaka.