An Open Label Post Licensure Trial to Evaluate the Safety and Immunogenicity of Indigenously Manufactured Killed Bivalent (O1 and O139) Whole Cell Oral Cholera Vaccine(Shanchol™)

Provision of safe water and food, establishment of adequate sanitation, and implementation of personal and community hygiene constitute the main public health interventions against cholera. These measures cannot be implemented fully in the near future in most cholera-endemic areas. Improvements to water and sanitation require substantial long-term investments, commitment from the local government, and often take years to implement. In the meantime, a safe, effective and affordable vaccine would be a useful tool for cholera prevention and control.

Considerable progress has been made during the last decade in the development of new generation oral vaccines against cholera. These have already been licensed in some countries and are now being considered for wider public health application. Cholera immunization is now recommended for travelers to high risk areas, refugee camps and for outbreak response. Furthermore, expanded use of cholera vaccines may be recommended for endemic areas, where there is increasing demand from both low- and middle-income populations.

Starting in the mid-1980s, following technology transfer from Prof Jan Holmgren, Vietnamese scientists at the National Institute of Hygiene and Epidemiology (NIHE) in Hanoi developed and produced an oral, killed cholera vaccine for the country's public health programs. A two-dose regimen of a first generation monovalent (anti-O1) cholera vaccine produced at US$ 0.10 per dose underwent a field trial in Hue, Vietnam. The study was not formally randomized: the vaccine was assigned on the basis of a systematic allocation scheme and the control group did not receive a placebo. The calculated efficacy against El Tor cholera was 66% in fully immunized adults and children. Protection against non-cholera was assessed and none was found suggesting a non-biased study design. Subsequently, killed 0139 whole cells were added to the Vietnamese vaccine due to the emergence of the new form of epidemic cholera caused by this serogroup. A study found the bivalent vaccine to be safe and immunogenic in adults and children one year and older.

The Vietnamese vaccine has several distinct advantages over the Swedish vaccine. The Vietnamese vaccine confers protection against the El Tor biotype in younger children. And the price of US $0.10 per dose is feasible for public health programs in developing countries, while the Swedish vaccine is prohibitively expensive. Finally, it can be administered without a buffer, while the Swedish vaccine requires a buffer and stricter cold chain requirements.

Since licensure of the oral cholera vaccine in Vietnam, more than 9 million doses have been administered without any report of serious adverse events. The vaccine is produced according to recommended guidelines at the Company for Vaccine and Biological Production No. 1 (VABIOTECH) in Hanoi. VABIOTECH is working towards WHO Good Manufacturing Practices (GMP) certification, which they hope to receive in the next few years. At the same time, the IVI and VABIOTECH have been working to internationalize the Vietnamese vaccine for global use. In order to comply with WHO requirements, the vaccine was reformulated.