Vaccines for Malaria: How Close Are We?

Malaria Research and Training Center, Faculty of Medicine, University of Bamako, Bamako, Mali, West Africa.
Annual review of medicine (Impact Factor: 12.93). 07/2011; 63(1):345-57. DOI: 10.1146/annurev-med-022411-192402
Source: PubMed


Vaccines are the most powerful public health tools mankind has created, but malaria parasites are bigger, more complicated, and wilier than the viruses and bacteria that have been conquered or controlled with vaccines. Despite decades of research toward a vaccine for malaria, this goal has remained elusive. Nevertheless, recent advances justify optimism that a licensed malaria vaccine is within reach. A subunit recombinant protein vaccine that affords in the neighborhood of 50% protective efficacy against clinical malaria is in the late stages of clinical evaluation in Africa. Incremental improvements on this successful vaccine are possible and worth pursuing, but the best hope for a highly efficacious malaria vaccine that would improve prospects for malaria eradication may lie with the use of attenuated whole parasites and powerful immune-boosting adjuvants.

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Available from: Christopher V Plowe,
    • "A malaria vaccine that prevents infection would reduce malaria morbidity and mortality and accelerate malaria eradication efforts [1]. Leading approaches for achieving this goal include subunit vaccines that target sporozoites and blood stage parasites and that block transmission of gametocytes to mosquitoes, as well as whole organism vaccines intended to block sporozoite invasion of liver cells, entirely preventing blood stage infection and gametocytogenesis [1] [2]. "
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    ABSTRACT: Prospects for malaria eradication will be greatly enhanced by an effective vaccine, but parasite genetic diversity poses a major impediment to malaria vaccine efficacy. In recent pre-clinical and field trials, vaccines based on polymorphic Plasmodium falciparum antigens have shown efficacy only against homologous strains, raising the specter of allele-specific immunity such as that which plagues vaccines against influenza and HIV. The most advanced malaria vaccine, RTS,S, targets relatively conserved epitopes on the P. falciparum circumsporozoite protein. After more than 40 years of development and testing, RTS,S, has shown significant but modest efficacy against clinical malaria in phase 2 and 3 trials. Ongoing phase 2 studies of an irradiated sporozoite vaccine will ascertain whether the full protection against homologous experimental malaria challenge conferred by high doses of a whole organism vaccine can provide protection against diverse strains in the field. Here we review and evaluate approaches being taken to design broadly cross-protective malaria vaccines.
    Vaccine 10/2015; DOI:10.1016/j.vaccine.2015.09.110 · 3.62 Impact Factor
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    • "This figure may be an under-estimation as a recent study has suggested that the global burden of malaria may be larger than previously estimated, with about 1.24 million deaths in 2010 [3] . One durable achievement that could crown the current malaria control strategies will be the development of a universal effective malaria vaccine [4] [5] [6] [7] . However, genetic diversity as well as antigenic variation in Plasmodium falciparum (P. "
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    ABSTRACT: To characterize the genetic diversity of Plasmodium falciparum (P. falciparum) field isolates in children from Lafia, North-central Nigeria, using the highly polymorphic P. falciparum merozoite surface protein 2 (MSP-2) gene as molecular marker. Three hundred and twenty children were enrolled into the study between 2005 and 2006. These included 140 children who presented with uncomplicated malaria at the Dalhatu Araf Specialist Hospital, Lafia and another 180 children from the study area with asymptomatic infection. DNA was extracted from blood spot on filter paper and MSP-2 genes were genotyped using allele-specific nested PCR in order to analyze the genetic diversity of parasite isolates. A total of 31 and 34 distinct MSP-2 alleles were identified in the asymptomatic and uncomplicated malaria groups respectively. No difference was found between the multiplicity of infection in the asymptomatic group and that of the uncomplicated malaria group (P>0.05). However, isolates of the FC27 allele type were dominant in the asymptomatic group whereas isolates of the 3D7 allele type were dominant in the uncomplicated malaria group. This study showed a high genetic diversity of P. falciparum isolates in North-central Nigeria and is comparable to reports from similar areas with high malaria transmission intensity.
    Asian Pacific Journal of Tropical Medicine 08/2013; 6(8):589-94. DOI:10.1016/S1995-7645(13)60102-9 · 0.93 Impact Factor
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    • "In spite of this advancement, falciparum malaria remains the most prevalent infectious disease resulting in a high level of morbidity and mortality [6]. The major reasons for this state is the lack of an appropriate vaccine [7,8] and the evolving phenomenon of anti-malarial drug resistance [9,10]. The gaps which still exist in understanding the biology of the parasite contribute, although to a lesser extent, to this state. "
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    ABSTRACT: Background The study of the Plasmodium falciparum heavy metal transporter gene pfmdr2 employed radioactive labelled heavy metal. As the use of radioactive isotopes shrank considerably during the last few years, resulting in the cessation of the production of some isotopes, amongst them Cadmium109 which was used for that purpose, a different approach had to be developed. Herein, a dual fluorescent labelling of heavy metals accumulation in the P. falciparum parasite is proposed as an alternative to the use of radioactive labelled heavy metals. Methods Plasmodium falciparum Cd resistant and sensitive strains at the trophozoite stage were used in this study. The cells were cultured at different CdCl2 concentrations and for different time periods followed by staining of the infected red blood cells with Fluo-3/AM for Cd detection and Hoechst 33342 for parasite DNA labelling. The fluorescent analysis was done by flow cytometry and confocal microscopy. Results The results show that the sensitive strain has a higher Fluo-3/AM fluorescence in a Cd concentration and time dependent manner, whereas in the resistant strain Fluo-3/AM fluorescence levels were negligible and increased only at high concentrations of Cd and at long incubation periods, but to a much lesser extent than the sensitive strain. No Cd uptake is observed in uninfected red blood cells populations originating from cultures infected with either sensitive or resistant strain. In addition, confocal microscopy overlay of Fluo-3/AM and Hoechst staining shows that the Cd metal accumulates in the parasite itself. Conclusions The dual fluorescent labelling is a valid method for detecting heavy metal accumulation in P. falciparum. Furthermore, in contrast to the use of radioactive labelled heavy metal, the fluorescent labelling enables us to differentiate between the different populations existing in a P. falciparum infected red blood cells cultures and thus actually study a phenomenon at the level of a single cell.
    Malaria Journal 11/2012; 11(1):371. DOI:10.1186/1475-2875-11-371 · 3.11 Impact Factor
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