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,
and 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 pneumococcus
and rotavirus 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
Background
Pneumonia and meningitis caused by Streptococcus
pneumoniae ("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 Haemophilus
influenzae 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 (Word
document 66kb).
Comments regarding the GAVI pneumococcal conjugate
R&D agenda can be sent by email to GAVIpneumo@who.int
Developing the R&D; activity
agenda for rotavirus oral vaccines
Background
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 < 5 years are
caused by rotavirus and in developing countries, about one child
in 250 will die of rotavirus diarrhoea by the age of 5 years. A
rotavirus vaccine is targeted to reduce this toll of illnesses,
hospitalizations and deaths.
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
Background
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.
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