GAVI agendas to accelerate the development and introduction of three vaccine products
At the Fourth GAVI Board Meeting in Noordwijk, The Netherlands in November 2000, the GAVI Board approved the recommendation from the Task Force on Research and Development that GAVI should focus initially on three vaccine products:
pneumococcal conjugate vaccines
rotavirus oral vaccines
meningococcal A (or A/C) conjugate vaccines
These three vaccine products were selected because of 1) their potential profound impact on childrens health, given the magnitude of the underlying disease burden (for
or the potential to cause epidemics (meningitis); and 2) their rather advanced status as "low-hanging fruits", i.e., their availability and use could be assured within five to seven years.
The GAVI Board asked that a team approach be used to address the scientific, operational and strategic gaps, in consultation with the existing and interested experts and parties including the other task forces. In order to initiate this process, two R&D; focal points were identified for each project by the GAVI Working Group:
Jay Wenger, WHO and Orin Levine, US NIH/CDC were tapped to lead the process of developing an R&D; agenda to assure affordability and use of pneumococcal conjugate vaccines for the developing world within seven years.
Roger Glass, CDC and Bernard Ivanoff, WHO were tapped to lead the process of developing an R&D; agenda to assure affordability and use of rotavirus oral vaccines for the developing world within seven years.
Gina Rabinovich, PATH and Luis Jodar, WHO were tapped to lead the process of developing an R&D; agenda to assure affordability and use of meningococcal A (or A/C) conjugate vaccines for the developing world within five years.
Developing the R&D; activity agenda for pneumococcal conjugate vaccine
Pneumonia and meningitis caused by
("pneumococcus") remains the most important cause of morbidity and mortality in young children throughout the world. Efforts have been underway to develop effective pneumococcal vaccines for almost a century. The US licensure of the first pneumococcal conjugate vaccine suitable for young infants in February 2000 represents a major milestone, as for the first time a vaccine is available that could prevent pneumococcal disease in the highest risk age group, infants under 12 months of age.
Experience over the past decade with
type b (Hib) vaccine has demonstrated that introduction of an effective new vaccine in industrialized countries does not automatically mean that the vaccine will be suitable for use in developing countries. Work must be done to define the burden of disease and the effectiveness of the vaccine in a developing country setting. Similar to Hib, the epidemiology and pathologies of pneumococcal disease are very different in developing countries compared to industrialized countries. This has several implications, including the facts that demonstration of disease burden and impact in industrialized countries is not sufficient to guarantee uptake in the developing world, and that the most effective way to use a vaccine differs between developing and industrialized countries.
Progress to date
The GAVI Task Force on Research and Development (TFRD) convened a
meeting of experts
in the area of pneumococcal disease and pneumococcal vaccination research on April 19-20, 2001, hosted by the US National Institutes of Health in Bethesda, MD. The meeting included approximately 40 representatives from academia, technical agencies, regulatory authorities and industry and included participants from 20 different countries.
Seven high priority activities in research and development were identified:
Developing a range of methods to assess key disease burden measures in different settings;
Standardizing diagnosis of pneumonia by chest x-ray;
Expanding surveillance for laboratory confirmed pneumococcal disease
Measuring the burden of pneumonia;
Establishing long-term surveillance to evaluate the impact of immunization;
Generating more local advocacy and ownership from existing and future research efforts.
Finding regulatory pathways appropriate for vaccines manufactured in US or Europe targeted for use in developing countries.
Download a complete copy of the GAVI R&D; priority activity list for pneumococcal conjugate vaccines (
Comments regarding the GAVI pneumococcal conjugate R&D agenda can be sent by email to
Developing the R&D; activity agenda for rotavirus oral vaccines
Rotavirus is the most common cause of severe diarrhoea among children worldwide. In both developed and developing countries, between 25-60% of all hospitalizations for childhood diarrhoea is for rotavirus. Roughly 5% of all deaths in children
The first rotavirus vaccine was licensed in the United States in August 1998 and was immediately recommended for the routine immunization of American children. Nearly 800,000 infants had been immunized when a small but significant number of episodes of intussusception (estimates ranging from 1 in 11,000 to 1 in 56,000) were identified in the two week period following the first dose of the vaccine. The recommendation for the vaccine has been withdrawn and the company has discontinued production.
While this unanticipated adverse event has blemished the name of rotavirus vaccines, it has demonstrated that live oral rotavirus vaccines can be effective in protecting infants against severe rotavirus diarrhoea and can be rapidly incorporated into a routine vaccination programme. To fill the gap created by the withdrawal of the first generation vaccine, several alternative vaccine candidates from global and local manufacturers are currently under active development.
Progress to date
A meeting was held in Geneva in May 2001, bringing together about 50 participants from more than 20 countries, including members from all GAVI Task Forces. Three working groups were charged with developing strategies to expedite rotavirus vaccine development , to promote access to vaccine, and to address issues of advocacy, epidemiology and country coordination.
In summary, development and testing in developing countries of a group of live oral rotavirus vaccines was identified as requiring the major investment. The importance of planning phase III trials powerful enough to detect rare adverse events such as intussuception was stressed. Given the experience with the
first generation vaccine
and of testing live oral vaccines, it was felt that the next generation of live oral vaccines could be ready within 3-5 years.
Furthermore, the strong interest of manufacturers in three developing countries (India, China, Indonesia) would help ensure that if successful, the next generation of vaccines might be available in large volume and at an affordable price. Investments would be needed in activities for advocacy and surveillance to prepare the groundwork of information so that policy makers, physicians, and people involved in immunization programmes are prepared to embrace the vaccine and introduce it into national immunization programmes.
Additional recommendations concerned consensus building, creating champions for the vaccine at many levels, working with advocacy groups, and expediting the introduction of the vaccine through demonstration projects in different regions.
Developing the R&D; activity agenda for meningococcal conjugate vaccines
Countries within the sub-Saharan African "meningitis belt" suffer from recurrent meningococcal epidemics, with a population at risk of over 200 million. During an epidemic, attack rates are high not only in infants but through young adulthood. The impact extends beyond the individual and epidemics are associated with social and economic chaos. The required public health interventions are disruptive, expensive and only partially effective. There are good reasons to believe that serogroup A/C meningococcal conjugate vaccine would provide long term protection in infants, induce immunological memory and reduce carriage, thus preventing epidemics and eliminating the need for disruptive emergency interventions.
Serogroup C meningococcal vaccines have been licensed and introduced in the United Kingdom. These vaccines have been shown to be highly effective in reducing meningococcal disease. The technology to produce a safe and effective serogroup A-containing meningococcal conjugate vaccine for Africa has been available for more than 10 years. Successful serogroup A/C conjugate prototypes previously evaluated in African infants were highly immunogenic, yet, largely due to commercial considerations, vaccine manufacturers halted the development of the bivalent (A/C) product.
Progress to date
The Meningitis Vaccine Project, a partnership between the World Health Organization (WHO) and the Program for Appropriate Technology in Health (PATH), was created with the objective to prevent and ultimately eliminate meningococcal epidemics in the African meningitis belt countries. The MVP was launched in May 20 and in July 2001 a director was appointed to manage and coordinate the activities of the partnership with core funding from the Bill and Melinda Gates Foundation of US $70 million over the next decade, in order to:
Develop a Mening A/C conjugate vaccine and evaluate it in Africa
Create a pathway for the licensure of vaccine which will be used largely in Africa
Assure production in sufficient volume to meet projected needs
Monitor throughout to assure the effectiveness and safety of the intervention
Finance the procurement of vaccine through existing or global programmes
Introduce the vaccine through mass and routine immunization in synergy with other public health programmes
The MVP is also developing a comprehensive package of activities for the next years including the development of a fast-track licensing clinical development plan, alternative licensing pathways for products that may not be registered in the country of production, standardisation and validation of serological assays, recommendations for quality control and production of meningococcal conjugate vaccines, development of a forecasting demand database, establishment of surveillance networks and laboratory capacity in countries of the meningitis belt, assessment of socio-economic impact of meningitis epidemics and development of a comprehensive regional plan with WHO AFRO for the introduction of these vaccines.
In parallel, the GAVI Financing Task Force, including its recently created "Out-of-the-Box Group", is advising the project on potential mechanisms to ensure the appropriate supply of vaccine once these vaccines are licensed. Finally, the GAVI Task Force on R&D; will hold a meeting in Africa to enumerate the R&D; activities required to achieve the goals of the Meningitis Vaccine Project.