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      Malaria Vaccines: Recent Advances and New Horizons

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          Abstract

          The development of highly effective and durable vaccines against the human malaria parasites Plasmodium falciparum and P. vivax remains a key priority. Decades of endeavor have taught that achieving this goal will be challenging; however, recent innovation in malaria vaccine research and a diverse pipeline of novel vaccine candidates for clinical assessment provides optimism. With first-generation pre-erythrocytic vaccines aiming for licensure in the coming years, it is important to reflect on how next-generation approaches can improve on their success. Here we review the latest vaccine approaches that seek to prevent malaria infection, disease, and transmission and highlight some of the major underlying immunological and molecular mechanisms of protection. The synthesis of rational antigen selection, immunogen design, and immunization strategies to induce quantitatively and qualitatively improved immune effector mechanisms offers promise for achieving sustained high-level protection.

          Abstract

          Development of highly effective vaccines against human malaria remains a public health priority. In this Review, Draper et al. describe the latest vaccine approaches to prevent malaria alongside immunological and molecular mechanisms of protection. Rational antigen selection, immunogen design, and novel immunization strategies offer promise for achieving high-level protection.

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          Live attenuated malaria vaccine designed to protect through hepatic CD8⁺ T cell immunity.

          Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8(+) T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8(+), IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.
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            Sterile protection against human malaria by chemoattenuated PfSPZ vaccine

            A highly protective malaria vaccine would greatly facilitate the prevention and elimination of malaria and containment of drug-resistant parasites. A high level (more than 90%) of protection against malaria in humans has previously been achieved only by immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (PfSPZ) inoculated by mosquitoes; by intravenous injection of aseptic, purified, radiation-attenuated, cryopreserved PfSPZ (‘PfSPZ Vaccine’); or by infectious PfSPZ inoculated by mosquitoes to volunteers taking chloroquine or mefloquine (chemoprophylaxis with sporozoites). We assessed immunization by direct venous inoculation of aseptic, purified, cryopreserved, non-irradiated PfSPZ (‘PfSPZ Challenge’) to malaria-naive, healthy adult volunteers taking chloroquine for antimalarial chemoprophylaxis (vaccine approach denoted as PfSPZ-CVac). Three doses of 5.12 × 104 PfSPZ of PfSPZ Challenge at 28-day intervals were well tolerated and safe, and prevented infection in 9 out of 9 (100%) volunteers who underwent controlled human malaria infection ten weeks after the last dose (group III). Protective efficacy was dependent on dose and regimen. Immunization with 3.2 × 103 (group I) or 1.28 × 104 (group II) PfSPZ protected 3 out of 9 (33%) or 6 out of 9 (67%) volunteers, respectively. Three doses of 5.12 × 104 PfSPZ at five-day intervals protected 5 out of 8 (63%) volunteers. The frequency of Pf-specific polyfunctional CD4 memory T cells was associated with protection. On a 7,455 peptide Pf proteome array, immune sera from at least 5 out of 9 group III vaccinees recognized each of 22 proteins. PfSPZ-CVac is a highly efficacious vaccine candidate; when we are able to optimize the immunization regimen (dose, interval between doses, and drug partner), this vaccine could be used for combination mass drug administration and a mass vaccination program approach to eliminate malaria from geographically defined areas.
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              Seven-Year Efficacy of RTS,S/AS01 Malaria Vaccine among Young African Children.

              The candidate malaria vaccine RTS,S/AS01 is being evaluated in order to inform a decision regarding its inclusion in routine vaccination schedules.
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                Author and article information

                Contributors
                Journal
                Cell Host Microbe
                Cell Host Microbe
                Cell Host & Microbe
                Cell Press
                1931-3128
                1934-6069
                11 July 2018
                11 July 2018
                : 24
                : 1
                : 43-56
                Affiliations
                [1 ]The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK
                [2 ]Center for Infectious Disease Research, 307 Westlake Ave N., Seattle, WA 98109, USA
                [3 ]PATH’s Malaria Vaccine Initiative (MVI), 455 Massachusetts Avenue NW, Suite 1000, Washington, DC 20001-2621, USA
                [4 ]Malaria Programme, Wellcome Sanger Institute, Cambridge, CB10 1SA, UK
                [5 ]Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK
                [6 ]Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA
                [7 ]Vaccine Research Center, NIAID/NIH, Bethesda, MD 20892, USA
                Author notes
                []Corresponding author simon.draper@ 123456ndm.ox.ac.uk
                Article
                S1931-3128(18)30320-2
                10.1016/j.chom.2018.06.008
                6054918
                30001524
                732782fd-dcc9-457f-af11-5b2028a3cd6b
                © 2018 The Author(s)

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

                History
                Categories
                Article

                Microbiology & Virology
                Microbiology & Virology

                Comments

                Malaria vaccine development collection topic 3) Vaccines in development:

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

                With the first-generation pre-erythrocytic vaccines aiming for licensure in the coming years, it is important to reflect on how next-generation approaches can improve on their success. Here, Draper and collaborators review the latest vaccine approaches that seek to prevent malaria infection, disease, and transmission and highlight some of the major underlying immunological and molecular mechanisms of protection. 

                2018-10-08 16:38 UTC
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