Article

Eliminating Epidemic Group A Meningococcal Meningitis In Africa Through A New Vaccine

Program for Appropriate Technology in Health,in Washington, DC, USA.
Health Affairs (Impact Factor: 4.64). 06/2011; 30(6):1049-57. DOI: 10.1377/hlthaff.2011.0328
Source: PubMed

ABSTRACT A new affordable vaccine against Group A meningococcus, the most common cause of large and often fatal African epidemics of meningitis, was introduced in Burkina Faso, Mali, and Niger in 2010. Widespread use of the vaccine throughout much of Africa may prevent more than a million cases of meningitis over the next decade. The new vaccine is expected to be cost-saving when compared to current expenditures on these epidemics; for example, an analysis shows that introducing it in seven highly endemic countries could save $350 million or more over a decade. International donors have already committed funds to support the new vaccine's introduction in Burkina Faso, Niger, and Mali, but an estimated US$400 million is needed to fund mass immunization campaigns in people ages 1-29 over six years in all twenty-five countries of the African meningitis belt. The vaccine's low cost--less than fifty cents per dose--makes it possible for the affected countries themselves to purchase vaccines for future birth cohorts.

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    • "Neisseria meningitidis is a major cause of epidemics in sub- Saharan Africa [1]. These were mainly caused by strains belonging to capsular group A, but there has been an increasing contribution of serogroups W and X strains with epidemic potential in the last two decades [2] [3] [4] [5]. A serogroup A polysaccharide conjugate vaccine (MenAfriVac) has been developed for preventive mass immunization in the African meningitis belt [6]. "
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    ABSTRACT: Neisseria meningitidis causes epidemics of meningitis in sub-Saharan Africa. These have mainly been caused by capsular group A strains, but W and X strains are increasingly contributing to the burden of disease. Therefore, an affordable vaccine that provides broad protection against meningococcal disease in sub-Saharan Africa is required. We prepared generalised modules for membrane antigens (GMMA) from a recombinant serogroup W strain expressing PorA P1.5,2, which is predominant among African W isolates. The strain was engineered with deleted capsule locus genes, lpxL1 and gna33 genes and over-expressed fHbp variant 1, which is expressed by the majority of serogroup A and X isolates. We screened nine W strains with deleted capsule locus and gna33 for high-level GMMA release. A mutant with five-fold increased GMMA release compared with the wild type was further engineered with a lpxL1 deletion and over-expression of fHbp. GMMA from the production strain had 50-fold lower ability to stimulate IL-6 release from human PBMC and caused 1000-fold lower TLR-4 activation in Human Embryonic Kidney cells than non-detoxified GMMA. In mice, the GMMA vaccine induced bactericidal antibody responses against African W strains expressing homologous PorA and fHbp v.1 or v.2 (geometric mean titres [GMT]=80,000-200,000), and invasive African A and X strains expressing a heterologous PorA and fHbp variant 1 (GMT=20-2500 and 18-5500, respectively). Sera from mice immunised with GMMA without over-expressed fHbp v.1 were unable to kill the A and X strains, indicating that bactericidal antibodies against these strains are directed against fHbp. A GMMA vaccine produced from a recombinant African N. meningitidis W strain with deleted capsule locus, lpxL1, gna33 and overexpressed fHbp v.1 has potential as an affordable vaccine with broad coverage against strains from all main serogroups currently causing meningococcal meningitis in sub-Saharan Africa.
    Vaccine 04/2014; 32(23). DOI:10.1016/j.vaccine.2014.03.068 · 3.49 Impact Factor
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    • "The Meningitis Vaccine Project (MVP) was established in 2001 as a joint effort between WHO (World Health Organization) and PATH (Program for Appropriate Technology in Health), with the aim to develop, test, license, and introduce meningococcal conjugate vaccines in sub-Saharan Africa [4] [5] [6]. As part of this mandate MVP developed a meningococcal group A conjugate vaccine that is manufactured by Serum Institute of India Ltd. (SIIL) and is now licensed, WHO prequalified, and used in mass vaccination campaigns in several meningitis belt countries [7] [13]. "
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    ABSTRACT: Group A Neisseria meningitidis epidemics have been an important and unresolved public health problem in sub-Saharan Africa for over a century. The Meningitis Vaccine Project (MVP) was established in 2001 with the goal of developing, testing, licensing, and introducing an affordable group A meningococcal conjugate vaccine for Africa. A monovalent group A conjugate vaccine, MenAfriVac™, was developed at the Serum Institute of India Ltd. and tested in clinical trials at multiple trial sites in sub-Saharan African countries. The setup and successful conduct of ICH-GCP standard vaccine trials across multiple trial sites located in low-resource settings are challenging. We describe the main operational issues encountered in three randomized, observer-blind, active controlled studies to evaluate the safety and immunogenicity of MenAfriVac™. The studies were conducted in parallel among 2700 subjects aged between 2 months and 29 years of age enrolled across four trial sites located in Mali, The Gambia, Senegal, and Ghana between September 2006 and August 2009. Many important lessons were learned during the preparation, setup, and implementation of the Meningitis Vaccine Project clinical program. They are summarized here to help vaccine development programs identify efficient pathways for successful implementation of clinical trials in low-resource settings.
    Vaccine 09/2012; 30(48). DOI:10.1016/j.vaccine.2012.09.008 · 3.49 Impact Factor
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    • "With a growing number of high quality vaccine producers and functional regulatory authorities in LMIC, and the success of strategies such as product development partnerships to develop and produce low cost safe vaccines for developing countries, as demonstrated with the meningococcal A conjugate vaccine in sub Saharan Africa in 2010 [16] [17] [18] [19], we can expect many more new vaccines to be manufactured, launched in, and exported from LMIC through mechanisms such as WHO prequalification [20]. The 2010 announcement of the Decade of Vaccines by the Bill and Melinda Gates Foundation set a number of new initiatives in motion. "
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    ABSTRACT: Confidence in vaccine safety is critical to national immunization strategies and to global public health. To meet the Millenium Development Goals, and buoyed by the success of new vaccines produced in developing countries, the World Health Organization has been developing a strategy to establish a global system for effective vaccine pharmacovigilance in all countries. This paper reports the findings of a qualitative survey, conducted for the WHO Global Vaccine Safety Blueprint project, on the perspectives of national regulatory authorities responsible for vaccine safety in manufacturing and procuring countries. Capacity and capabilities of detecting, reporting and responding to adverse events following immunization (AEFI), and expectations of minimum capacity necessary for vaccine pharmacovigilance were explored. Key barriers to establishing a functional national vaccine safety system in developing countries were identified. The lack of infrastructure, information technology for stable communications and data exchange, and human resources affect vaccine safety monitoring in developing countries. A persistent "fear of reporting" in several low and middle income countries due to insufficient training and insecure employment underlies a perceived lack of political will in many governments for vaccine pharmacovigilance. Regulators recommended standardized and internationally harmonized safety reporting forms, improved surveillance mechanisms, and a global network for access and exchange of safety data independent of industry.
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