Targets of complement-fixing antibodies in protective immunity against malaria in children
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Date
2019
Authors
Reiling, L.
Boyle, M.J.
White, M.T.
Wilson, D.W.
Feng, G.
Weaver, R.
Opi, D.H.
Persson, K.E.M.
Richards, J.S.
Siba, P.M.
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Journal article
Citation
Nature Communications, 2019; 10(1):610-1-610-13
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Linda Reiling, Michelle J. Boyle, Michael T. White, Danny W. Wilson, Gaoqian Feng, Rupert Weaver, D. Herbert Opi, Kristina E.M. Persson, Jack S. Richards, Peter M. Siba, Freya J.I. Fowkes, Eizo Takashima, Takafumi Tsuboi, Ivo Mueller, James G. Beeson
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Abstract
Antibodies against P. falciparum merozoites fix complement to inhibit blood-stage replication in naturally-acquired and vaccine-induced immunity; however, specific targets of these functional antibodies and their importance in protective immunity are unknown. Among malaria-exposed individuals, we show that complement-fixing antibodies to merozoites are more strongly correlated with protective immunity than antibodies that inhibit growth quantified using the current reference assay for merozoite vaccine evaluation. We identify merozoite targets of complement-fixing antibodies and identify antigen-specific complement-fixing antibodies that are strongly associated with protection from malaria in a longitudinal study of children. Using statistical modelling, combining three different antigens targeted by complement-fixing antibodies could increase the potential protective effect to over 95%, and we identify antigens that were common in the most protective combinations. Our findings support antibody-complement interactions against merozoite antigens as important anti-malaria immune mechanisms, and identify specific merozoite antigens for further evaluation as vaccine candidates.
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© The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.