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Merozoite surface proteins in red blood cell invasion, immunity and vaccines against malaria

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      Abstract

      Malaria accounts for an enormous burden of disease globally, with Plasmodium falciparum accounting for the majority of malaria, and P. vivax being a second important cause, especially in Asia, the Americas and the Pacific. During infection with Plasmodium spp., the merozoite form of the parasite invades red blood cells and replicates inside them. It is during the blood-stage of infection that malaria disease occurs and, therefore, understanding merozoite invasion, host immune responses to merozoite surface antigens, and targeting merozoite surface proteins and invasion ligands by novel vaccines and therapeutics have been important areas of research. Merozoite invasion involves multiple interactions and events, and substantial processing of merozoite surface proteins occurs before, during and after invasion. The merozoite surface is highly complex, presenting a multitude of antigens to the immune system. This complexity has proved challenging to our efforts to understand merozoite invasion and malaria immunity, and to developing merozoite antigens as malaria vaccines. In recent years, there has been major progress in this field, and several merozoite surface proteins show strong potential as malaria vaccines. Our current knowledge on this topic is reviewed, highlighting recent advances and research priorities.

      Abstract

      The authors summarize current knowledge of merozoite surface proteins of malaria parasites; their function in invasion, processing of surface proteins before, during and after invasion, their importance as targets of immunity, and the current status of malaria vaccines that target merozoite surface proteins.

      Abstract

      Graphical Abstract Figure.

      The authors summarize current knowledge of merozoite surface proteins of malaria parasites; their function in invasion, processing of surface proteins before, during and after invasion, their importance as targets of immunity, and the current status of malaria vaccines that target merozoite surface proteins.

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      Most cited references 319

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      Vivax malaria: neglected and not benign.

      Plasmodium vivax threatens almost 40% of the world's population, resulting in 132-391 million clinical infections each year. Most of these cases originate from Southeast Asia and the Western Pacific, although a significant number also occurs in Africa and South America. Although often regarded as causing a benign and self-limiting infection, there is increasing evidence that the overall burden, economic impact, and severity of disease from P. vivax have been underestimated. Malaria control strategies have had limited success and are confounded by the lack of access to reliable diagnosis, emergence of multidrug resistant isolates, the parasite's ability to transmit early in the course of disease and relapse from dormant liver stages at varying time intervals after the initial infection. Progress in reducing the burden of disease will require improved access to reliable diagnosis and effective treatment of both blood-stage and latent parasites, and more detailed characterization of the epidemiology, morbidity, and economic impact of vivax malaria. Without these, vivax malaria will continue to be neglected by ministries of health, policy makers, researchers, and funding bodies.
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        Comparative genomics of the neglected human malaria parasite Plasmodium vivax.

        The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.
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          Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial.

          (2015)
          The efficacy and safety of the RTS,S/AS01 candidate malaria vaccine during 18 months of follow-up have been published previously. Herein, we report the final results from the same trial, including the efficacy of a booster dose.
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            Author and article information

            Affiliations
            [1 ]Burnet Institute for Medical Research and Public Health, 85 Commercial Road, Melbourne, Victoria, Australia
            [2 ]Department of Microbiology, Monash University, Clayton, Victoria, Australia
            [3 ]Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
            [4 ]Department of Epidemiology and Preventive Medicine, Monash University, Clayton, Victoria, Australia
            [5 ]School of Population Health, University of Melbourne, Parkville, Victoria, Australia
            Author notes
            [* ] Corresponding author: Centre for Biomedical Research, Burnet Institute of Medical Research and Public Health, 85 Commercial Road, Melbourne 3004, Victoria, Australia. Tel: +61-3-9282-2111; Fax: +61-3-9282-2265; E-mail: beeson@ 123456burnet.edu.au
            Journal
            FEMS Microbiol Rev
            FEMS Microbiol. Rev
            femsre
            femsre
            FEMS Microbiology Reviews
            Oxford University Press
            0168-6445
            1574-6976
            01 February 2016
            May 2016
            01 February 2016
            : 40
            : 3
            : 343-372
            26833236 4852283 10.1093/femsre/fuw001
            © FEMS 2016.

            This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

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            Pages: 30
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            Review Article
            Custom metadata
            May 2016

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