- Licensure paves way for global use of first IVI-developed vaccine

A boy is immunized with the oral cholera vaccine, which was
developed by the International Vaccine Institute, in Kolkata, India.

A new oral cholera vaccine developed by the International Vaccine Institute (IVI) has been licensed in India, paving the way for worldwide use of a low-cost cholera vaccine suitable for use in developing countries, where most cholera cases occur.

 “The licensure of the vaccine in India, where the national regulatory authority is approved by the World Health Organization (WHO), paves the way for a wider use of the vaccine in cholera-endemic populations in Asia and elsewhere,” said Dr. John Clemens, Director-General of the IVI. “We are delighted that the vaccine will be produced by Shantha Biotechnics, in Hyderabad, a company with a strong record of supplying high-quality vaccines to United Nations agencies, such as UNICEF.”

Cholera remains an important public health problem in the developing world. In 2007, 177,963 cholera cases and 4,031 deaths were reported to WHO from 53 countries, with 94 percent of cases reported from Africa. The true figures are likely to be much higher, due to underreporting, and as many as 120,000 deaths are estimated to occur each year from the disease. A recent outbreak in Zimbabwe has killed at least 4,200 since last August.

Despite recommendations from WHO for the use of new-generation oral cholera vaccines in 2001,  no country has yet introduced cholera vaccines into its immunization program, with the exception of Vietnam, which has been using a locally produced oral cholera vaccine since 1997 following technology transfer from Swedish scientists. There is only one internationally licensed oral cholera vaccine that is currently available. But this vaccine, Dukoral® produced by Crucell/SBL Vaccines, is too expensive at around $20 per dose for developing country populations who need the vaccine the most, and has been used mainly by travelers from developed countries.

The Vietnamese vaccine (ORC-Vac), while inexpensive, safe, and effective, has not been internationally accepted since the drug regulatory authority of Vietnam has not yet satisfied WHO´s requirements. Seeing the need for making a low-cost oral cholera vaccine internationally available, the IVI targeted the Vietnamese vaccine for expanded use. However, an analysis of this vaccine showed that for it to comply with WHO guidelines, the vaccine needed to be reformulated and its production technology modified.

IVI scientists worked with the Vietnamese producer, VaBiotech, to develop a killed whole cell cholera vaccine that meets WHO´s quality standards. The improved vaccine was shown to be safe and immunogenic through studies in adults and children in Vietnam and India. The IVI, in collaboration with the National Institute of Cholera and Enteric Diseases (NICED) of India, is conducting a large Phase III trial of the improved oral cholera vaccine in the urban slums of Kolkata to determine its efficacy in a cholera-endemic population. The study, which began in July 2006, enrolled approximately 67,000 individuals. Initial results of this analysis found that the vaccine conferred substantial protection during two years of follow-up, including protection of children aged 1–5 years.

“The use of safe and effective cholera vaccines in cholera-endemic areas could lead to a significant and rapid decline in cholera incidence and, ultimately, to its control worldwide,” said Dr. Clemens.

In order for this vaccine to be used outside of Vietnam and sold to UN organizations, however, it must be produced in countries where the national regulatory authority has met WHO´s requirements. As such, the IVI transferred the production technology to the vaccine manufacturer, Shantha Biotechnics, based in India. Shantha obtained the licensure for this vaccine (now called Shanchol) on February 24, 2009 from the Drug Controller General of India, the Indian national regulatory authority.

The approval of the vaccine is a result of the IVI’s Cholera Vaccine Initiative (CHOVI), a program of research supported by the Bill and Melinda Gates Foundation and by the governments of Korea and Sweden. Launched in late 2006 the CHOVI builds upon the achievements of the IVI’s Diseases of the Most Impoverished (DOMI) Program, which was also supported by the Gates Foundation. CHOVI aims to accelerate the introduction of safe and effective modern cholera vaccines to populations in high-risk cholera areas.