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This article is part of the Research Topic

Immunity to Malaria and Vaccine Strategies

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01254

Functional comparison of blood-stage Plasmodium falciparum malaria vaccine candidate antigens

 Joseph J. Illingworth1*, Daniel G. Alanine1, Rebecca E. Brown1, Jennifer Marshall1,  Helen E. Bartlett1, Sarah Silk1, Genevieve M. Labbe1, Doris Quinkert1, Jee Sun Cho1, Jason P. Wendler2,  David J. Pattinson1,  Lea Barfod1,  Alexander Douglas1, Michael Shea1, Katherine E. Wright3, Simone C. de Cassan1, Matthew K. Higgins3 and  Simon J. Draper1*
  • 1Jenner Institute, Nuffield Department of Medicine, University of Oxford, United Kingdom
  • 2Wellcome Trust Centre for Human Genetics (WT), United Kingdom
  • 3Department of Biochemistry, Medical Sciences Division, University of Oxford, United Kingdom

The malaria genome encodes over 5000 proteins and many of these have also been proposed to be potential vaccine candidates, although few of these have been tested clinically. RH5 is one of the leading blood-stage Plasmodium falciparum malaria vaccine antigens and Phase I/II clinical trials of vaccines containing this antigen are currently underway. Its likely mechanism of action is to elicit antibodies that can neutralize merozoites by blocking their invasion of red blood cells (RBC). However, many other antigens could also elicit neutralizing antibodies against the merozoite, and most of these have never been compared directly to RH5. The objective of this study was to compare a range of blood stage antigens to RH5, to identify any antigens that outperform or synergize with anti-RH5 antibodies. We selected 55 gene products, covering 15 candidate antigens that have been described in the literature and 40 genes selected on the basis of bioinformatics functional prediction. We were able to make 20 protein-in-adjuvant vaccines from the original selection. Of these, S-antigen and CyRPA, robustly elicited antibodies with neutralizing properties. Anti-CyRPA IgG generally showed additive GIA with anti-RH5 IgG, although high levels of anti-CyRPA-specific rabbit polyclonal IgG were required to achieve 50 % GIA. Our data suggest that further vaccine antigen screening efforts are required to identify a second merozoite target with similar antibody-susceptibility to RH5.

Keywords: Malaria, Blood stage malaria, Vaccine, antigen, Neutralising antibodies, Antibodies, Merozoite, RH5

Received: 21 Dec 2018; Accepted: 17 May 2019.

Edited by:

Julius Clemence Hafalla, London School of Hygiene and Tropical Medicine (LSHTM), United Kingdom

Reviewed by:

Adrian J. Luty, Institut de recherche pour le développement (IRD), France
Philippe Boeuf, Burnet Institute, Australia
Takafumi Tsuboi, Ehime University, Japan  

Copyright: © 2019 Illingworth, Alanine, Brown, Marshall, Bartlett, Silk, Labbe, Quinkert, Cho, Wendler, Pattinson, Barfod, Douglas, Shea, Wright, de Cassan, Higgins and Draper. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Joseph J. Illingworth, Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, England, United Kingdom, joejamesillingworth@gmail.com
Prof. Simon J. Draper, Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7DQ, England, United Kingdom, simon.draper@ndm.ox.ac.uk