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Synergistic malaria vaccine combinations identified by systematic antigen screening

Bustamante, LY; Powell, GT; Lin, Y-C; Macklin, MD; Cross, N; Kemp, A; Cawkill, P; ... Rayner, JC; + view all (2017) Synergistic malaria vaccine combinations identified by systematic antigen screening. PNAS - Proceedings of the National Academy of Sciences of the United States of America , 114 (45) pp. 12045-12050. 10.1073/pnas.1702944114. Green open access

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Abstract

A highly effective vaccine would be a valuable weapon in the drive toward malaria elimination. No such vaccine currently exists, and only a handful of the hundreds of potential candidates in the parasite genome have been evaluated. In this study, we systematically evaluated 29 antigens likely to be involved in erythrocyte invasion, an essential developmental stage during which the malaria parasite is vulnerable to antibody-mediated inhibition. Testing antigens alone and in combination identified several strain-transcending targets that had synergistic combinatorial effects in vitro, while studies in an endemic population revealed that combinations of the same antigens were associated with protection from febrile malaria. Video microscopy established that the most effective combinations targeted multiple discrete stages of invasion, suggesting a mechanistic explanation for synergy. Overall, this study both identifies specific antigen combinations for high-priority clinical testing and establishes a generalizable approach that is more likely to produce effective vaccines.

Type: Article
Title: Synergistic malaria vaccine combinations identified by systematic antigen screening
Open access status: An open access version is available from UCL Discovery
DOI: 10.1073/pnas.1702944114
Publisher version: http://doi.org/10.1073/pnas.1702944114
Language: English
Additional information: Copyright © 2017 the Author(s). Published by PNAS. This is an open access article distributed under the PNAS license.
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, malaria, vaccine, Plasmodium falciparum, antigen combinations, erythrocyte invasion, PLASMODIUM-FALCIPARUM, ERYTHROCYTE INVASION, PROTEIN, ANTIBODIES, COMPLEX, PFRH5, PROTECTION, RESISTANCE, DIVERSITY, CANDIDATE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: http://discovery.ucl.ac.uk/id/eprint/10048049
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