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: 4.97). 06/2011; 30(6):1049-57. DOI: 10.1377/hlthaff.2011.0328
Source: PubMed


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.
    Full-text · Article · Apr 2014 · Vaccine
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    • "A new NmA polysaccharide-tetanus toxoid conjugated vaccine, MenAfriVac, developed to eliminate NmA epidemics in the meningitis belt, was first introduced on a national scale in Burkina Faso [17-21]. Following a pilot introduction in the district of Kaya in September 2010, the whole 1-29-year-old population in Burkina Faso was vaccinated in December 2010 [21]. "
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    ABSTRACT: The conjugate vaccine against serogroup A Neisseria meningitidis (NmA), MenAfriVac, was first introduced in mass vaccination campaigns of the 1-29-year-olds in Burkina Faso in 2010. The aim of this study was to genetically characterize meningococcal isolates circulating in Burkina Faso before and up to 13 months after MenAfriVac mass vaccination. A total of 1,659 meningococcal carriage isolates were collected in a repeated cross-sectional carriage study of the 1-29-year-olds in three districts of Burkina Faso in 2010 and 2011, before and up to 13 months after mass vaccination. Forty-two invasive isolates were collected through the national surveillance in Burkina Faso in the same period. All the invasive isolates and 817 carriage isolates were characterized by serogroup, multilocus sequence typing and porA-fetA sequencing. Seven serogroup A isolates were identified, six in 2010, before vaccination (4 from carriers and 2 from patients), and one in 2011 from an unvaccinated patient; all were assigned to sequence type (ST)-2859 of the ST-5 clonal complex. No NmA carriage isolate and no ST-2859 isolate with another capsule were identified after vaccination. Serogroup X carriage and disease prevalence increased before vaccine introduction, due to the expansion of ST-181, which comprised 48.5 % of all the characterized carriage isolates. The hypervirulent serogroup W ST-11 clone that was responsible for most of meningococcal disease in 2011 and 2012 was not observed in 2010; it appeared during the epidemic season of 2011, when it represented 40.6 % of the serogroup W carriage isolates. Successive clonal waves of ST-181 and ST-11 may explain the changing epidemiology in Burkina Faso after the virtual disappearance of NmA disease and carriage. No ST-2859 strain of any serogroup was found after vaccination, suggesting that capsule switching of ST-2859 did not occur, at least not during the first 13 months after vaccination.
    Full-text · Article · Aug 2013 · BMC Infectious Diseases
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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.
    Full-text · Article · Sep 2012 · Vaccine
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