ORAL CHOLERA VACCINE:

First licensed vaccine developed with Gates Foundation support
 
   

Efforts to accelerate the global use of new generation cholera vaccines gained significant momentum with the licensure of a new oral cholera vaccine, Shanchol™ (pictured) in India in 2009.



IVI scientists developed this vaccine, with funding from the Bill & Melinda Gates Foundation, the Government of Korea, and the Swedish International Development Cooperation Agency (SIDA), by significantly modifying a vaccine used and produced only in Vietnam so that it meets international Good Manufacturing Practice (GMP) standards and WHO production guidelines.

Following field trials in India and Vietnam showing the new vaccine to be safe and immunogenic in both adults and children, IVI scientists transferred the technology for the vaccine to Shantha Biotechics of Hyderabad, India - a producer of high-quality, affordable vaccines and a major vaccine supplier to UNICEF. Shanchol™ is the first new vaccine to be developed and licensed with funding from the Gates Foundation, as well as the first licensed vaccine developed by the IVI.

The IVI aims to make this vaccine available for use in public health programs in India and other cholera-affected countries in Asia and Africa to control endemic cholera, as well as to help control large-scale outbreaks. The vaccine has three major advantages for use in developing countries over the only other cholera vaccine currently on the market (Dukoral®), which is mainly used by travelers from developed countries.

First, it does not require administration with a buffer, thereby greatly simplifying its use under field conditions, including in refugee camps and other post-crisis situations. Second, it will be available to governments and international agencies at low cost (e.g., ≈$1.00 per dose with sufficient demand). Third, a large efficacy trial taking place in India is showing that the vaccine is more effective and lasts longer in young children (1-5 years old) than Dukoral®). Shantha is applying to WHO for pre-qualification of this vaccine to allow its purchase by United Nations agencies, including UNICEF, and to facilitate its use in other countries. Shanchol™ consists of killed whole cells from a mix of pathogenic strains of V. cholerae (O1 and O139) and is given in two doses one to six weeks apart. The vaccine is licensed for use in adults and children one year and older. The trial in Kolkata, which enrolled nearly 70,000 people, has shown that the vaccine provides 67 percent protection for at least two years in this highly-endemic population. Continued surveillance and analysis will determine if the vaccine protects for a longer period of time and if it confers herd protection to non-vaccinated neighbors of the vaccines.

Growing momentum for use of oral cholera vaccines

The licensing in India of Shanchol™ has added considerably to the momentum for the use of oral cholera vaccines to control endemic and epidemic cholera. The increased interest among policymakers in cholera immunization has also been prompted by the increased frequency of large, protracted and often uncontrolled cholera epidemics in Zimbabwe and other African and Asian countries in the past few years, and by fears that cholera incidence and severity is increasing, due to global warming, growing urbanization, and the increasing strain that urban migration and growth in slums are putting on already inadequate water and sanitation systems.

Staff from Shantha Biotechnics undergoing training in the fermentation of cholera bacteria at the IVI as part of the technology transfer program for the manufacture and quality control testing of the new inactivated oral cholera vaccine.


In April 2009 policymakers in India decided in a meeting (pictured) organized by the IVI and India's National Institute of Cholera and Enteric Diseases (NICED) to conduct a pilot cholera vaccination program in a highly cholera-endemic rural area of Orissa, using the Shanchol™ vaccine. They reached the decision based on evidence of increased incidence of the disease in India, the two-year results of the efficacy trial of this vaccine taking place in Kolkata, and other evidence. The pilot program, supported by the Gates Foundation, will assess the feasibility, population demand for, and cost of cholera vaccination delivered through the government's immunization program. Policymakers will use the results of this pilot project to help decide whether and how to introduce cholera vaccination in high-risk areas of the country. The government of Bangladesh, in collaboration with the research institute, ICDDR,B, has also decided to conduct a cholera vaccination demonstration project in a large section of Dhaka, where many cholera cases have been found. The study, also funded by the Gates Foundation, will involve vaccinating around 120,000 children and adults using the Shanchol™ vaccine.



The study will compare the effectiveness of vaccination (against a control group) and of household water treatment methods and health promotion activities. The IVI is providing technical assistance for the project. The government of Bangladesh views this study as a critical step in setting policy for the use of cholera vaccines through the country's National Programme on Immunization. At the international level, the Merieux Foundation and the IVI organized a meeting on Integrating Vaccines into Global Cholera Control Efforts in Annecy, France in April 2009. Participants, who included policymakers; representatives of technical, humanitarian and donor agencies; and scientists called for the use of oral cholera vaccines, including the new Shanchol™ vaccine, to control endemic cholera and prevent outbreaks, along with traditional cholera control efforts (e.g., water and sanitation improvements). At the international level, the Merieux Foundation and the IVI organized a meeting on Integrating Vaccines into Global Cholera Control Efforts in Annecy, France in April 2009. Participants, who included policymakers; representatives of technical, humanitarian and donor agencies; and scientists called for the use of oral cholera vaccines, including the new Shanchol™ vaccine, to control endemic cholera and prevent widespread outbreaks, along with traditional cholera control efforts(e.g., water, sanitation improvements)

Of critical importance, the WHO Strategic Advisory Group of Experts (SAGE), which plays a key role in making recommendations to WHO on the introduction of new vaccines, held a session on cholera vaccines at its meeting in October 2009. The results of much of the IVI's work in cholera - including disease burden and economic studies, the laboratory and clinical development of the Shanchol™ vaccine, and vaccine trials and demonstration projects - were presented during the session and in a background paper prepared for the meeting. Two IVI staff members also served on the ad hoc Working Group on Cholera Vaccines that prepared the paper and presentations for the meeting. As a result of this meeting, WHO will issue new, updated recommendations for the use of cholera vaccines in a Position Paper to be published in 2010. These recommendations should help stimulate increased interest among countries in using cholera vaccines in high-risk areas, and among donor and technical agencies in supporting their use.