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Theoretical Implications of a Pre-Erythrocytic Plasmodium vivax Vaccine for Preventing Relapses

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      Abstract

      Preventing malaria infection through vaccination requires preventing every sporozoite inoculated by mosquito bite: a major challenge for Plasmodium falciparum. Plasmodium vivax sporozoites consist of tachysporozoites causing primary infection and bradysporozoites leading to relapses. We hypothesise that a candidate P. vivax vaccine with low efficacy against primary infection may substantially reduce transmission by preventing relapses.

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      Most cited references 12

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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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        Randomized, double-blind, phase 2a trial of falciparum malaria vaccines RTS,S/AS01B and RTS,S/AS02A in malaria-naive adults: safety, efficacy, and immunologic associates of protection.

         Jack Williams,  F Cummings,   (2009)
        To further increase the efficacy of malaria vaccine RTS,S/AS02A, we tested the RTS,S antigen formulated using the AS01B Adjuvant System (GlaxoSmithKline Biologicals). In a double-blind, randomized trial, 102 healthy volunteers were evenly allocated to receive RTS,S/AS01B or RTS,S/AS02A vaccine at months 0, 1, and 2 of the study, followed by malaria challenge. Protected vaccine recipients were rechallenged 5 months later. RTS,S/AS01B and RTS,S/AS02A were well tolerated and were safe. The efficacy of RTS,S/AS01B and RTS,S/AS02A was 50% (95% confidence interval [CI], 32.9%-67.1%) and 32% (95% CI, 17.6%-47.6%), respectively. At the time of initial challenge, the RTS,S/AS01B group had greater circumsporozoite protein (CSP)-specific immune responses, including higher immunoglobulin (Ig) G titers, higher numbers of CSP-specific CD4(+) T cells expressing 2 activation markers (interleukin-2, interferon [IFN]-gamma, tumor necrosis factor-alpha, or CD40L), and more ex vivo IFN-gamma enzyme-linked immunospots (ELISPOTs) than did the RTS,S/AS02A group. Protected vaccine recipients had a higher CSP-specific IgG titer (geometric mean titer, 188 vs 73 mug/mL; P < .001), higher numbers of CSP-specific CD4(+) T cells per 10(6) CD4(+) T cells (median, 963 vs 308 CSP-specific CD4(+) T cells/10(6) CD4(+) T cells; P < .001), and higher numbers of ex vivo IFN-gamma ELISPOTs (mean, 212 vs 96 spots/million cells; P < .001). At rechallenge, 4 of 9 vaccine recipients in each group were still completely protected. The RTS,S/AS01B malaria vaccine warrants comparative field trials with RTS,S/AS02A to determine the best formulation for the protection of children and infants. The association between complete protection and immune responses is a potential tool for further optimization of protection. Trial registration. ClinicalTrials.gov identifier NCT00075049.
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          Intravital microscopy demonstrating antibody-mediated immobilisation of Plasmodium berghei sporozoites injected into skin by mosquitoes.

          Previous studies have shown that mosquitoes inject Plasmodium sporozoites into avascular portions of the skin of their rodent host rather than directly into the blood circulation. Then, over time, these sporozoites move into the circulation, from where they reach the liver to initiate a malaria infection. By use of intravital microscopy of the skin, we present direct morphological evidence of mosquito probing that introduces sporozoites into avascular tissue, of the migration of these sporozoites through the dermis and into blood vessels, and of the role of anti-sporozoite antibodies in blocking sporozoite invasion of these dermal blood vessels.
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            Author and article information

            Affiliations
            [1 ]MRC Centre for Outbreak Analysis & Modelling, Department of Infectious Disease Epidemiology, Imperial College London, UK
            [2 ]Division of Population Health & Immunity, Walter and Eliza Hall Institute, Melbourne, Australia
            [3 ]Department of Parasites & Insect Vectors, Institut Pasteur, Paris, France
            Author notes
            Contributors
            Journal
            Trends Parasitol
            Trends Parasitol
            Trends in Parasitology
            Elsevier Science
            1471-4922
            1471-5007
            1 April 2017
            April 2017
            : 33
            : 4
            : 260-263
            28077251
            5380217
            S1471-4922(16)30234-3
            10.1016/j.pt.2016.12.011
            © 2017 The Authors

            This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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            Parasitology

            hypnozoite, plasmodium vivax, malaria, vaccine, relapse

            Comments

            Malaria vaccine development collection topic 5) Identifying and developing the new generation of malaria vaccines - Making use of mathematical modelling:

            See https://www.scienceopen.com/collection/malariavaccine

             

            White and colleagues applied a mathematical model of within-host hypnozoite infection coupled to a model of transmission between humans and mosquitoes to investigate the theoretical implications of using vaccination to inhibit the build-up of the hypnozoite reservoir.

            2018-10-08 17:58 UTC
            +1

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