Put an end to a century of epidemics
Meningococcal meningitis has plagued sub-Saharan Africa for more than a century. We can stop it and put an end to the sufferings caused by this deadly and devastating disease, but our dream can become reality only if adequate resources are available to introduce MenAfriVac®—the new meningococcal A conjugate vaccine developed through the Meningitis Vaccine Project—on a large scale in all the countries of the meningitis belt. MenAfriVac is manufactured by Serum Institute of India, Ltd. (SIIL).
In July, SIIL submits the pediatric license variation dossier in parallel to
Indian regulatory authorities and the World Health Organization prequalification team.
Isolated meningitis A cases are reported in Guinea where MenAfriVac has not yet been introduced. No group A meningitis case has been reported among the 153 million individuals who received MenAfriVac in 2010‒2013.
Médecins sans Frontières administers MenAfriVac to some 77,000 people in refugee camps in South Sudan and Chad.
In February, the journal Vaccine publishes results from the first MenAfriVac campaign conducted without constant refrigeration, showing that the new approach succeeded in provided complete and safe coverage of the population with significant advantages in terms of logistics. A separate study in the Bulletin of the World Health Organization finds that cutting out the cold chain can halve vaccine storage and transportation costs.
Sudan completes the second (and last) phase of the MenAfriVac campaign while Nigeria completes its third (and penultimate) campaign. MenAfriVac is further deployed in The Gambia, which vaccinates the whole of its target population in one go; and in Ethiopia, where vaccination campaigns will continue in 2014 and 2015. Some countries organize mop-up vaccination campaigns for nomadic populations and people who live in refugee camps. In all, more than 50 million people receive MenAfriVac in 2013, bringing the total number of vaccinees to more than 153 million in the African meningitis belt since vaccine launch in 2010.
In September, the medical journal The Lancet publishes a study on the dramatic impact of MenAfriVac in Chad where the incidence of meningitis dropped by 94% following a mass immunization campaign in 2011. Carriage of the disease-causing bacteria also was also dramatically reduced following vaccination with MenAfriVac.
A June report by the WHO indicates that the number of meningitis cases reported so far during the 2012‒2013 meningitis season is at the lowest level in a decade. The decrease is thought to be due to the progressive introduction of MenAfriVac in the African meningitis belt.
Cameroon and Chad complete their vaccination while Nigeria continues to roll out MenAfriVac. The vaccine is introduced in four new countries—Benin, Ghana, Senegal, and Sudan. By the end of 2012 more than 100 million people are vaccinated against meningitis A. Pharmacovigilance activities conducted in the ten countries that introduced MenAfriVac continue to indicate that the vaccine is very safe.
MenAfriVac receives regulatory approval to be kept outside the cold chain for up to four days at up to 40°C, in a controlled temperature chain (CTC). A pilot project using the CTC approach is conducted in Benin in November as part of the mass vaccination campaign. The pilot is conducted jointly by the Government of Benin, WHO/AFRO, MVP, and Optimize—the WHO-PATH collaboration leading the CTC activities. MenAfriVac is the first vaccine intended for use in Africa approved for this type of use, setting a regulatory path for other heat-stable vaccines. The new flexibility could also potentially increase vaccination campaign efficiency and coverage across the meningitis belt.
The Phase 3 infant study PsA-TT-007 is launched in Mali.
In December 2011, Cameroon, Chad, and Nigeria become the fourth, fifth, and sixth countries in the African meningitis belt to introduce MenAfriVac at large scale. Some 21 million people are vaccinated in the three countries. Mali and Niger complete the last phase of their own vaccination campaigns as well, boosting the total number vaccinated to almost 55 million. Pharmacovigilance activities conducted in the six countries that introduced MenAfriVac in 2010 and 2011 continue to indicate that the vaccine is very safe.
By the end of the 2010–2011 meningitis season, Burkina Faso, Mali, and Niger report no meningococcal A cases among the nearly 20 million people who received one dose of MenAfriVac during the September and December 2010 mass vaccination campaigns.
A persistence study is launched in Mali, Senegal, and the Gambia.
On 6 December MenAfriVac is introduced at large scale in Burkina Faso, Mali, and Niger. By year’s end, more than 19.5 million people are immunized with the new vaccine. Pharmacovigilance activities conducted in the three countries indicate that MenAfriVac is a very safe vaccine.
MenAfriVac is introduced at pilot scale in September in Burkina Faso, Mali, and Niger, protecting more than one million people from group A meningococcal meningitis.
The World Health Organization prequalifies MenAfriVac. Prequalification is a process that guarantees that individual vaccines meet international standards of quality, safety, and efficacy.
The Maharahstra state Food and Drug Administration grants Serum Institute of India Ltd. (SIIL) the marketing authorization enabling the MenA conjugate vaccine, to be exported and used in Africa. This decision approves a December 2009 request by the Drugs Controller General of India (DCGI)—the national authority that regulates market authorization of vaccines developed in India—that MenAfriVac be made available for meningitis belt countries in Africa.
PsA-TT-005 (Phase 3 lot consistency study) is launched in India.
PsA-TT-006 (Phase 3 safety study) is launched in Mali.
Lumbar puncture around 1950. The same technique is used today for meningitis diagnosis.
Fears that a new epidemic wave may have started in Africa turn out to be true as 78,890 suspected cases and 4,243 deaths are reported during the epidemic season. The humanitarian organization Médecins Sans Frontières (MSF) launches its largest mass vaccination campaign ever, deploying up to 400 emergency vaccination teams to vaccinate 7.5 million people in Chad, Niger, and Nigeria.
The new case-based surveillance system is piloted in some districts in Burkina Faso.
SIIL submits the MenA vaccine regulatory file to the Drugs Controller General of India (DCGI) for Indian licensure and to the World Health Organization (WHO) for prequalification.
Preparations are made for PsA-TT-005 (lot-to-lot consistency study in India) and PsA-TT-006 (safety study in Africa).
The African Meningococcal Carriage Consortium (MenAfriCar) is created as a result of the 2005 WHO carriage meeting. Led by the London School of Hygiene and Tropical Medicine, MenAfriCar is the largest, most concerted effort to date to better understand how meningococcal meningitis is spread in Africa. MenAfriCar will work closely with MVP in the years to come.
A total of 33,381 suspected meningitis cases and 3,276 deaths are reported from Africa.
SIIL prepares consistency lots for the Phase 3 study (PsA-TT-005) and makes good progress on the development of the regulatory file.
Guidelines for case-based surveillance are developed. Under the "old" system, suspected cases of meningitis were reported. With the new guidelines, confirmed cases with complete descriptions of epidemiological and laboratory characteristics will be reported.
The Phase 2 infant study PsA-TT-004 is launched in Ghana.
Science publishes a 6-page feature story on meningitis and the development of a MenA conjugate vaccine for Africa.
Agence de Médecine Préventive completes a study on the perception and socioeconomic impact of meningitis in Burkina Faso. The study systematically analyzes the significant burden meningitis imposes on families and health systems.
A total of 45,997 suspected meningitis cases and 4,150 deaths are reported from Africa—26,878 cases from Burkina Faso alone, forcing the government to make a plea for international assistance. The appeal is positively received, and US$3 million is collected for emergency vaccination campaigns.
SIIL and MVP develop a strategic plan for vaccine licensure and production.
SIIL prepares the clinical lot for the infant study and starts compiling data for the regulatory file to be submitted to the Drugs Controller General of India (DCGI) for Indian licensure of the MenA conjugate vaccine.
Week 4 results from PsA-TT-002, the pivotal Phase 2 clinical study, show that the MenA conjugate vaccine is safe and highly immunogenic. As a result, Phase 2/3 studies PsA-TT-003 and PsA-TT-003a are launched.
The Michael & Susan Dell Foundation pledges US$4 million to support vaccine introduction in Burkina Faso.
The Norwegian Research Council funds the Norwegian Institute of Public Health to carry out carriage studies. This is a collaborative project with the US Centers for Disease Control and Prevention (CDC), MVP, WHO/AFRO, and the Burkina Faso Ministry of Health.
Rockhopper TV produces a documentary film on the 2007 epidemic as part of the BBC series Kill or Cure. The program shows the realities of meningitis in Africa.
A total of 41,526 suspected meningitis cases and 3,967 deaths are reported from Africa. The international community fears that the significant number of cases signals the start of a new epidemic wave in Africa. Six million people are vaccinated with polysaccharide vaccines. The direct cost of these emergency mass vaccination campaigns in Burkina Faso alone is evaluated at US$3.5 million (5 percent of the country's annual health expenditures).
SIIL completes the construction of the new building where the MenA vaccine will be produced.
One-year follow-up data from PsA-TT-001 show the vaccine to be safe and immunogenic.
The MVP pivotal Phase 2 trial, PsA-TT-002, is launched. The study looks at safety and immunogenicity of the MenA conjugate vaccine in the younger age-group targeted by the mass vaccination campaigns.
Dr. Luis G. Sambo, the new director of the WHO regional office in Africa, attends the fifth Project Advisory Group (PAG) meeting in Brazzaville, Congo, and assures MVP of his full support to the project.
A total of 18,311 suspected meningitis cases and 2,581 deaths are reported from Africa.
The first clinical trial, PsA-TT-001, is launched. This Phase 1 trial evaluates the safety and immunogenicity of the MenA conjugate vaccine in 74 healthy adults in India.
SIIL prepares additional batches of MenA conjugate for Phase 2 clinical trials and stability studies.
Standard operating procedures are finalized for enhanced meningitis surveillance in belt countries.
WHO undertakes a retrospective analysis of two decades of epidemiological data in Burkina Faso, Mali, and Niger, while experts meet in Geneva to explore ways to fund and carry out comprehensive meningococcal carriage studies in Africa.
Strategies for the comprehensive introduction of the MenA conjugate vaccine in sub-Saharan Africa are agreed upon at a workshop in Ouagadougou, Burkina Faso.
A total of 31,712 suspected meningitis cases and 4,123 deaths are reported from Africa.
PATH enters into a long-term sublicense and supply agreement with SIIL to develop, test, and produce clinical and commercial lots of MenA conjugate vaccine at a target price of US$0.40 per dose.
INTOX Pvt Ltd. conducts toxicology and local tolerance testing of the candidate vaccine that shows that the product has no deleterious effects in animals.
SIIL prepares test lots and the first batches of the MenA conjugate vaccine.
Partnerships are established with laboratories at the U.S. Centers for Disease Control and Prevention (CDC) and the U.K. Health Protection Agency (HPA) for the serology testing for the clinical trials.
MVP and consultants develop a clinical development plan to evaluate the safety and immunogenicity of the MenA conjugate vaccine.
The first pre-award agreements are signed.
MVP and scientific consultants define a timeline for pharmaceutical operations, including training, conjugation technology transfer, clinical batches preparation, and scale-up.
MVP and consultants support the work of the two suppliers in improving their purification methods, and MVP leads the transfer of a conjugation technology from Center for Biologics Evaluation and Research (CBER) to SIIL. CBER transfers the conjugation technology to SIIL in December.
The MVP clinical team visits potential clinical sites. At each site, capacity is reviewed in terms of ability to conduct clinical studies, and the MVP team meets with representatives of local and national health authorities.
MVP provides financial support for enhanced surveillance of meningitis in Africa. The Multi-Disease Surveillance Center in Ouagadougou, Burkina Faso, produces the first detailed bulletins of the meningitis situation in three meningitis belt countries and reports 8,256 suspected cases and 1,985 deaths. From this point on, weekly epidemic bulletins are published by WHO/AFRO in Ouagadougou.
It becomes clear that no manufacturer in the developed world can produce a MenA conjugate vaccine at less than US$0.50 per dose.
MVP starts exploring alternative strategies for the development of such a vaccine and identifies: (a) suppliers of the two major vaccine components, (b) a collaborator for the development and transfer of a conjugation technology that "conjugates" (chemically links) the two components together, and (c) a developing-country vaccine manufacturer willing to manufacture an affordable MenA conjugate vaccine (Serum Institute of India Ltd. [SIIL]).
MVP puts in place a product development plan consisting of a pharmaceutical, clinical, and regulatory strategy for the development of the meningococcal A (MenA) conjugate vaccine. This plan is approved by the Expert Panel and the Project Advisory Group (PAG), which meets for the first time in Abuja, Nigeria.
MVP develops a distinct visual identity with a logo and website.
The Gates Foundation awards PATH and WHO US$70 million for the development of meningitis vaccines in Africa. Dr. F. Marc LaForce is appointed as the Project Director for MVP, and the project is established in the PATH office in Ferney-Voltaire, France.
Preliminary discussions are held with African public health officials who make it clear that a cost of more than US$0.50 per dose would be unsustainable.
Enhanced surveillance activities are started in three meningitis belt countries.
Pharmaceutical companies are approached to discuss the development of affordable conjugate meningococcal vaccines for use in Africa.
WHO draws up a plan for the development of conjugate vaccines to fight and eliminate meningitis epidemics in Africa. Delegates from African and Eastern Mediterranean countries, multilateral organizations, vaccine manufacturers, and the scientific community gather at WHO and conclude that:
- Meningococcal disease is a major public health problem.
- Current strategies that focus on epidemic response or preparedness are insufficient.
- Development of a conjugate vaccine for Africa is a high priority.
By the end of the year, plans are drawn for the creation of the Meningitis Vaccine Project (MVP) via a collaboration between WHO and PATH.
More than 25,000 people die during the largest meningococcal meningitis epidemic ever recorded in history. More than 250,000 cases are reported to the WHO.
Conjugate vaccines better adapted to Africa are field-tested in Niger and the Gambia, but the projects are discontinued in the mid-1990s.
Polysaccharide vaccines are developed in response to epidemics of meningitis in industrialized countries, but their effectiveness remains limited in Africa.
Major epidemic outbreaks are observed in Africa, especially in the sub-Saharan region, where they continue to wreak havoc.
Neisseria meningitidis is identified as the causative agent of bacterial meningococcal meningitis.
Scientists describe meningococcal disease for the first time during an outbreak in Geneva, Switzerland.
Photo: Association Amicale Santé Navale et d'Outre-Mer.