Children play at an IVI research site in Kolkata, India

IVI’s efforts to control cholera have gained momentum with the launch of the Cholera Vaccine Initiative (CHOVI) in late 2006. This new Initiative hopes to accelerate the introduction of safe and effective modern cholera vaccines to populations in cholera-endemic regions, as well as to prevent cholera epidemics during natural or man-made emergencies.

While the development and widespread use of oral rehydration therapy (ORT) has greatly reduced cholera deaths in the past 30 years, the disease continues to be a scourge in many developing countries, killing an estimated 120,000 people world-wide each year. 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 world-wide.

The Initiative, which builds upon the achievements of the Cholera Program of the Diseases of the Most Impoverished (DOMI) Program Read more about DOMI, is made possible through a $22 million grant from the Bill & Melinda Gates Foundation.

CHOVI focuses on the development, technology transfer and field testing of two new-generation oral cholera vaccines: 1) a two-dose killed whole-cell (WC) vaccine developed in Vietnam and improved with technical assistance from IVI; and 2) a one-dose live attenuated Peru 15-vaccine.

In order for the Vietnamese WC vaccine to be used beyond Vietnam and sold to UN organizations, it must be pre-qualified by the World Health Organization (WHO) and produced in countries where the national regulatory authority has been approved by WHO. Since Vietnam does not yet meet these conditions, CHOVI is “internationalizing” the vaccine by coordinating the transfer of production technology to two high-quality producers — Shantha Biotechnics of India and BioFarma of Indonesia. Both India and Indonesia have WHO-approved national regulatory authorities for vaccines, which will ensure the internationalization of the locally-produced WC vaccines. Both producers also have a strong record of supplying high-quality vaccines to UN agencies, such as UNICEF.

“Successful technology transfer of this vaccine to these producers will help ensure the availability on the world market of a low-cost, high-quality oral cholera vaccine appropriate for use by public health programs in endemic countries," said Dr. Luis Jodar, IVI’s Deputy Director-General.

CHOVI will also conduct the studies needed for licensure of the vaccine in India and Indonesia. These studies include a three-year randomized, controlled efficacy trial that began last July under the DOMI Program in Kolkata, India, using the bulk vaccine from Vietnam that was fill/finished by Shantha in India Read a related story. They also include “bridging” studies in India and Indonesia to demonstrate the safety and immunogenicity of the vaccine produced from scratch in both countries, once technology transfer has been completed.

The ultimate aim of this activity is to have the whole-cell vaccine produced by Shantha and BioFarma pre-qualified by WHO so that it can be sold to UN agencies and for use in endemic countries.

For the second cholera vaccine — the oral live attenuated Peru-15 vaccine, IVI is implementing a clinical development plan to move the vaccine from the lab to its use in populations at risk of endemic or epidemic cholera. Peru-15, which requires only one dose, has been developed by the U.S. producer, AVANT Immunotherapeutics, under the brand name, Choleragarde®. CHOVI will conduct Phase II studies in Bangladesh and India to evaluate the safety and immunogenicity of the vaccine in adults, including HIV-positive persons in Kolkata, and in children, when co-administered with measles at nine months of age.

These studies will be followed by a large-scale Phase III randomized, placebo-controlled trial of the vaccine in persons nine months and older in Matlab, Bangladesh. Surveillance will take place for three years following vaccination to measure the vaccine’s efficacy.

The aim is to have the Peru-15 vaccine licensed in India and Bangladesh for its use in public health programs in both of these cholera-endemic countries. The project will also set the stage for the pre-qualification of the vaccine by WHO for its broader use in other endemic countries and by UN agencies.

If CHOVI’s activities lead to the widespread use of these two modern cholera vaccines in cholera-endemic areas — especially with the help of WHO and other UN agencies — the Initiative may help pave the way for the eventual control of this ancient scourge.