Malaria vaccines since 2000: progress, priorities, products.
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ABSTRACT:
SUBMITTER: Duffy PE
PROVIDER: S-EPMC7283239 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:There have been significant decreases in malaria mortality and morbidity in the last 10-15 years, and the most advanced pre-erythrocytic malaria vaccine, RTS,S, received a positive opinion from European regulators in July 2015. However, no blood-stage vaccine has reached a phase III trial. The first part of this review summarizes the pros and cons of various assays and models that have been and will be used to predict the efficacy of blood-stage vaccines. In the second part, blood-stage vaccine candidates that showed some efficacy in human clinical trials or controlled human malaria infection models are discussed. Then, candidates under clinical investigation are described in the third part, and other novel candidates and strategies are reviewed in the last part.
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Project description:BackgroundAs more countries progress towards malaria elimination, a better understanding of the most critical health system features for enabling and supporting malaria control and elimination is needed.MethodsAll available health systems data relevant for malaria control were collated from 23 online data repositories. Principal component analysis was used to create domain specific health system performance measures. Multiple regression model selection approaches were used to identify key health systems predictors of progress in malaria control in the 2000-2016 period among 105 countries. Additional analysis was performed within malaria burden groups.ResultsThere was large heterogeneity in progress in malaria control in the 2000-2016 period. In univariate analysis, several health systems factors displayed a strong positive correlation with reductions in malaria burden between 2000 and 2016. In multivariable models, delivery of routine services and hospital capacity were strongly predictive of reductions in malaria cases, especially in high burden countries. In low-burden countries approaching elimination, primary health center density appeared negatively associated with progress while hospital capacity was positively correlated with eliminating malaria.ConclusionsThe findings presented in this manuscript suggest that strengthening health systems can be an effective strategy for reducing malaria cases, especially in countries with high malaria burden. Potential returns appear particularly high in the area of service delivery.
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Project description:Malaria is a life-threatening disease and one of the main causes of morbidity and mortality in the human population. The disease also results in a major socio-economic burden. The rapid spread of malaria epidemics in developing countries is exacerbated by the rise in drug-resistant parasites and insecticide-resistant mosquitoes. At present, malaria research is focused mainly on the development of drugs with increased therapeutic effects against Plasmodium parasites. However, a vaccine against the disease is preferable over treatment to achieve long-term control. Trials to develop a safe and effective immunization protocol for the control of malaria have been occurring for decades, and continue on today; still, no effective vaccines are available on the market. Recently, peptide-based vaccines have become an attractive alternative approach. These vaccines utilize short protein fragments to induce immune responses against malaria parasites. Peptide-based vaccines are safer than traditional vaccines, relatively inexpensive to produce, and can be composed of multiple T- and B-cell epitopes integrated into one antigenic formulation. Various combinations, based on antigen choice, peptide epitope modification and delivery mechanism, have resulted in numerous potential malaria vaccines candidates; these are presently being studied in both preclinical and clinical trials. This review describes the current landscape of peptide-based vaccines, and addresses obstacles and opportunities in the production of malaria vaccines.
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Project description:Sanaria Inc. has developed methods to manufacture, purify and cryopreserve aseptic Plasmodium falciparum (Pf) sporozoites (SPZ), and is using this platform technology to develop an injectable PfSPZ-based vaccine that provides high-grade, durable protection against infection with Pf malaria. Several candidate vaccines are being developed and tested, including PfSPZ Vaccine, in which the PfSPZ are attenuated by irradiation, PfSPZ-CVac, in which fully infectious PfSPZ are attenuated in vivo by concomitant administration of an anti-malarial drug, and PfSPZ-GA1, in which the PfSPZ are attenuated by gene knockout. Forty-three research groups in 15 countries, organized as the International PfSPZ Consortium (I-PfSPZ-C), are collaborating to advance this program by providing intellectual, clinical, and financial support. Fourteen clinical trials of these products have been completed in the USA, Europe and Africa, two are underway and at least 12 more are planned for 2015-2016 in the US (four trials), Germany (2 trials), Tanzania, Kenya, Mali, Burkina Faso, Ghana and Equatorial Guinea. Sanaria anticipates application to license a first generation product as early as late 2017, initially to protect adults, and a year later to protect all persons >6 months of age for at least six months. Improved vaccine candidates will be advanced as needed until the following requirements have been met: long-term protection against natural transmission, excellent safety and tolerability, and operational feasibility for population-wide administration. Here we describe the three most developed whole PfSPZ vaccine candidates, associated clinical trials, initial plans for licensure and deployment, and long-term objectives for a final product suitable for mass administration to achieve regional malaria elimination and eventual global eradication.
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Project description:Viral vectors used in heterologous prime-boost regimens are one of very few vaccination approaches that have yielded significant protection against controlled human malaria infections. Recently, protection induced by chimpanzee adenovirus priming and modified vaccinia Ankara boosting using the ME-TRAP insert has been correlated with the induction of potent CD8(+) T cell responses. This regimen has progressed to field studies where efficacy against infection has now been reported. The same vectors have been used pre-clinically to identify preferred protective antigens for use in vaccines against the pre-erythrocytic, blood-stage and mosquito stages of malaria and this work is reviewed here for the first time. Such antigen screening has led to the prioritization of the PfRH5 blood-stage antigen, which showed efficacy against heterologous strain challenge in non-human primates, and vectors encoding this antigen are in clinical trials. This, along with the high transmission-blocking activity of some sexual-stage antigens, illustrates well the capacity of such vectors to induce high titre protective antibodies in addition to potent T cell responses. All of the protective responses induced by these vectors exceed the levels of the same immune responses induced by natural exposure supporting the view that, for subunit vaccines to achieve even partial efficacy in humans, "unnatural immunity" comprising immune responses of very high magnitude will need to be induced.
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Project description:The understanding of the genetic basis of neurological disorders has grown rapidly in the last two decades. Despite the genomic heterogeneity within African populations, large-scale candidate gene or linkage and exome studies are lacking. However, current knowledge on neurogenetics in African populations is limited and geographically very uneven. Isolated reports indicate the existence of autosomal dominant or recessive conditions incorporating cerebrovascular, movement, neuromuscular, seizure and motor neuron disorders in Africans. In addition, few African families with neurodegenerative disorders associated with dementia have been characterized in North, West and South Africa. The current insurgency in genomic research triggered by among others the Human Health and Heredity (H3) Africa Initiative indicates that there are unique opportunities to advance our knowledge and understanding of the influence of genomic variation on the pattern, presentations and prognosis of neurological disorders in Africa. These have enormous potential to unmask novel genes and molecular pathways germane to the neurobiology of brain disorders. It would facilitate the development of novel diagnostics, preventative and targeted treatments in the new paradigm of precision medicine. Nevertheless, it is crucial to strike a balance between effective traditional public health strategies and personalized genome based care. The translational barriers can be overcome through robust stakeholder engagement and sustainable multilevel, multigenerational and multidisciplinary capacity building and infrastructural development for genomic medicine in Africa.
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