Background
In July 2006, the Gates Foundation awarded IVI a $20 million grant to implement the Cholera Vaccine Initiative ("CHOVI"), building upon the achievements of the DOMI Cholera Program. The aim of this Initiative is to control cholera by developing and deploying safe and effective oral cholera vaccines in populations at risk for endemic or epidemic cholera. The Initiative will focus on the development and field testing of two oral cholera vaccines:

1) A newly-reformulated killed whole-cell (WC) vaccine

The oral cholera WC vaccine was developed in Vietnam through technology transfer from Gothenburg University in Sweden and is currently being produced in Vietnam to prevent cholera outbreaks. The vaccine, which requires two doses, was reformulated with assistance from IVI scientists to comply with WHO standards and has successfully undergone Phase II trials in Vietnam and India.(See the DOMI cholera program) To enable this low-cost cholera vaccine to be sold on the world market for use throughout the world, CHOVI is assisting with technology transfer of the vaccine to two highly-qualified producers in Asia: Shantha Biotechnics of India and BioFarma of Indonesia. Both countries have WHO-approved national regulatory authorities for vaccines, which will ensure the quality of the locally-produced WC vaccines. Both manufacturers also produce vaccines that have been pre-qualified by WHO for sale to UNICEF and other UN agencies. Successful technology transfer of this vaccine to these producers will help assure the availability of the world market of a low-cost, high-quality oral cholera vaccine appropriate for use by public health programs in endemic countries, as well as for the establishment of a WHO cholera vaccine stockpile for use in emergencies;

2) A newer generation live, attenuated Peru-15 strain vaccine

Goals
The goals of CHOVI are to:

• Help create a cost-competitive supply of killed whole-cell (WC) oral cholera vaccine for use in endemic countries and for emergency situations by completing technology transfer of the vaccine to Shantha Biotechnics in India and BioFarma in Indonesia and by providing technical assistance for the clinical testing, local licensure and WHO-pre-qualification of the vaccine;

• Assist with the implementation of a clinical development plan of the live oral Peru-15 cholera vaccine, including the conduct of Phase II and III clinical trials in India and Bangladesh and application for national licensure in both countries.

Projects

Technology transfer, evaluation and regulatory approval of killed whole-cell vaccine

CHOVI is assisting with technology transfer of the Vietnamese WC vaccine to Shantha and BioFarma that was begun under the DOMI Cholera Program. The Initiative is also conducting the studies needed for in-country licensure of the vaccine in India and Indonesia. These include continuing post-vaccination surveillance for the randomized, controlled Phase III efficacy trial in Kolkata, India, through which nearly 70,000 persons one year and older were vaccinated in mid-2006 with the cholera vaccine or a placebo in three slum areas of the city.(See the DOMI cholera program) The vaccine used in the Kolkata trial was bulk vaccine from Vietnam that was fill/finished by Shantha. CHOVI will also assist with bridging studies in India and Indonesia to demonstrate the safety and immunogenicity of the vaccine produced from scratch by Shantha and BioFarma once technology transfer is completed. The ultimate aim of this activity is to have the whole-cell vaccine produced by Shantha and BioFarma pre-qualified by WHO to enable its sale to UN agencies and for establishment of a WHO emergency stockpile.

Clinical development plan for Peru-15 cholera vaccine candidate

A series of field trials will take place in Bangladesh and India for the reformulated Peru-15 vaccine (Choleragard®). The trials will include a series of Phase II studies in Matlab, Bangladesh and Kolkata, India to evaluate the safety and immunogenicity of the reformulated vaccine in adults, including HIV-positive persons in Kolkata and in children (when given at nine months of age concomitantly with measles). There will then be 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 of this activity is to have the Peru-15 vaccine licensed in both India and Bangladesh for its use in public health programs in both of these cholera-endemic countries. The project also plans to set the stage for the pre-qualification of the vaccine by WHO for its broader use in other endemic countries and by UN agencies.

Collaborators on CHOVI

• AVANT Immunotherapeutics, Needham, MA, USA
• BioFarma, Indonesia
• ICDDR,B, Dhaka, Bangladesh
• National Institute of Cholera and Enteric Diseases (NICED), Kolkata, India
• Shantha Biotechnics, Hyderabad, India
• World Health Organization

Last Updated : May 2007