Background
In October 2007, the Bill & Melinda Gates Foundation provided a seven-year grant to the IVI to implement the Vi-based Vaccines for Asia (VIVA) Initiative. VIVA builds upon the achievements of the DOMI Typhoid Program in five Asian countries, which revealed continued high rates of typhoid fever in several study sites (see paper in the Bulletin of WHO), a substantial demand for new-generation typhoid vaccines among populations in high-risk areas, and the feasibility of both school-based and community-based vaccination using the single-dose injectable Vi polysaccharide vaccine in these largely impoverished settings (See the DOMI Typhoid Program page). In collaboration with Dr. John Robbins' laboratory at the U.S. National Institutes of Health (NIH), the IVI has also developed a Vi conjugate vaccine, which uses diphtheria toxoid (DT) as the protein carrier. Unlike the Vi polysaccharide, the Vi conjugate vaccine, is expected to be effective in infants and can therefore be included in the infant immunization schedule.

Dr Greg Smith, IVI's Production and Quality Control Coordinator, working on the development of a Vi-DT conjugate vaccine at the IVI laboratories. The vaccine, developed in collaboration with U.S. National Institutes Health, is being transferred to Shantha Biotechnics in Hyderabad, India.

The aim of the VIVA Initiative is to reduce typhoid fever mortality and morbidity in infants and children in typhoid-endemic countries by accelerating the adoption of Vi vaccines and the technical development, clinical evaluation and licensure of affordable Vi conjugate vaccines. This Initiative will help to set the stage for countries and technical agencies to implement the updated WHO recommendations on typhoid vaccines issued in February 2008, which call for typhoid vaccination of children in high-risk areas of endemic countries using new-generation vaccines (Wkly Epidemiol Rec).

Goals
The goals of the VIVA Initiative are to:

• Ensure a cost-competitive supply of Vi polysaccharide vaccine for introduction in high-risk typhoid-endemic areas by completing the transfer of technology or ensuring fill/finish capacity at selected manufacturers; and ensuring regulatory approvals at the country level and subsequent WHO pre-qualification;

• Ensure the licensure of a Vi conjugate vaccine by transferring the Vi-DT conjugate vaccine technology from the IVI's laboratories to a selected developing country producer and assisting with the clinical development program for licensure of the vaccine;

• Accelerate the adoption of Vi vaccine in high-risk areas in two large typhoid-endemic Asian countries by implementing large-scale, school-based pilot Vi introduction projects in Indonesia and Pakistan, and evaluating the disease impact, feasibility and financial sustainability of the pilot introduction projects;

• Pave the way for the introduction of typhoid vaccines in immunization programs of developing countries by preparing an investment case and advocacy strategy for typhoid vaccination.

Projects

Technical transfer of high-yield Vi polysaccharide vaccine to qualified developing country producers

IVI laboratories have optimized the growth of S. Typhi Ty2, resulting in a greater than three-fold increase in the yield of Vi (See abstract in the Journal of Biotechnology) This should lead to a reduction in the costs of producing the vaccine. The production technology for the high-yield Vi is being transferred to Shantha Biotechnics of Hyderabad, India and other high-quality producers in developing countries.

Technology transfer and evaluation of Vi-diphtheria toxoid (DT) conjugate vaccine

In collaboration with the U.S. NIH, IVI laboratories have developed a Vi-DT conjugate vaccine. The conjugation method has demonstrated excellent consistency, and optimal loading of the diphtheria toxoid on the Vi polysaccharide has been performed. The production technology for the vaccine is being transferred to Shantha Biotechnics, which was selected following a rigorous due diligence process. VIVA will assist with the clinical development of the vaccine for licensure in India and for eventual pre-qualification by WHO. The aim of this program is to develop a safe, effective and affordable Vi conjugate vaccine for use by public health programs in typhoid-endemic countries.

Pilot introduction of Vi polysaccharide vaccine in two Asian countries

VIVA is supporting the pilot introduction of Vi vaccine in two typhoid-endemic Asian countries - Pakistan and Indonesia. These pilot projects were requested by the governments in each country, based on the results of the DOMI surveillance studies, which showed high rates of typhoid fever in children in North Jakarta, Indonesia and Karachi, Pakistan. The pilot projects will involve school-based "catch-up" vaccination campaigns for primary school children and will assess the feasibility, impact on clinical disease and sustainability of mass typhoid vaccination in the pilot areas. An innovative financing mechanism, in which vaccination of private school students, who are charged a reasonable user fee, will cross-subsidize free public school vaccination, will also be tested in the pilot projects. These pilot introduction projects are seen as the first step in the targeted roll-out of typhoid vaccination in high-risk areas in each country.

Preparation of an investment case and advocacy strategy for targeted typhoid vaccination

With the growing number of new and upcoming vaccines that countries can consider for introduction into their immunization programs, governments and donor organizations increasingly require solid analysis of the need for and value of each vaccine they are considering. VIVA is preparing an "investment case" that will synthesize data on the burden of typhoid disease; forecast the anticipated demand for and use of typhoid vaccines in high-risk areas; and estimate the expected public health impact, cost and cost-effectiveness of expanded typhoid vaccination. VIVA will also implement a communications/advocacy strategy to disseminate the results of the pilot introduction projects and investment case analyses.

IVI Scientist, Leon Ochiai (behind), with children in Karachi, Pakistan, where the pilot introduction of typhoid Vi vaccine is taking place as part of the VIVA Initiative.

Collaborators:

• U.S. National Institutes of Health
• Aga Khan University Hospital, Karachi, Pakistan
• Centers for Disease Control, Ministry of Health, Indonesia
• National Institute of Health Research and Development, Ministry of Health, Indonesia
• Amson Vaccines and Pharma (PVT) Ltd, Pakistan
• Bharat Biotech International Ltd, India
• Shantha Biotechnics Ltd, India
• sanofi pasteur

Last Updated : June 2008