Targets of complement-fixing antibodies in protective immunity against malaria in children

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

doi:10.1038/s41467-019-08528-z

Targets of complement-fixing antibodies in protective immunity against malaria in children

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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	610
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-08528-z
Publication status	Published - 2019 Feb 5

Subject classification (UKÄ)

Immunology in the medical area
Infectious Medicine

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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., Fowkes, F. J. I., Takashima, E., Tsuboi, T., Mueller, I., & Beeson, J. G. (2019). Targets of complement-fixing antibodies in protective immunity against malaria in children. Nature Communications, 10(1), [610]. https://doi.org/10.1038/s41467-019-08528-z

@article{7db6b5cfc75341e0a2bb7c1b9d0f3eed,

title = "Targets of complement-fixing antibodies in protective immunity against malaria in children",

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.",

author = "Linda Reiling and Boyle, {Michelle J.} and White, {Michael T.} and Wilson, {Danny W.} and Gaoqian Feng and Rupert Weaver and Opi, {D. Herbert} and Persson, {Kristina E.M.} and Richards, {Jack S.} and Siba, {Peter M.} and Fowkes, {Freya J.I.} and Eizo Takashima and Takafumi Tsuboi and Ivo Mueller and Beeson, {James G.}",

year = "2019",

month = feb,

day = "5",

doi = "10.1038/s41467-019-08528-z",

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

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T1 - Targets of complement-fixing antibodies in protective immunity against malaria in children

AU - Reiling, Linda

AU - Boyle, Michelle J.

AU - White, Michael T.

AU - Wilson, Danny W.

AU - Feng, Gaoqian

AU - Weaver, Rupert

AU - Opi, D. Herbert

AU - Persson, Kristina E.M.

AU - Richards, Jack S.

AU - Siba, Peter M.

AU - Fowkes, Freya J.I.

AU - Takashima, Eizo

AU - Tsuboi, Takafumi

AU - Mueller, Ivo

AU - Beeson, James G.

PY - 2019/2/5

Y1 - 2019/2/5

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-019-08528-z

DO - 10.1038/s41467-019-08528-z

M3 - Article

C2 - 30723225

AN - SCOPUS:85061147634

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 610

ER -

Targets of complement-fixing antibodies in protective immunity against malaria in children

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