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

被引：63
|
作者：
Reiling, Linda [1 ]
Boyle, Michelle J. [1 ]
White, Michael T. [2 ]
Wilson, Danny W. [1 ,3 ]
Feng, Gaoqian [1 ,4 ,5 ]
Weaver, Rupert [1 ]
Opi, D. Herbert [1 ,6 ,7 ]
Persson, Kristina E. M. [8 ]
Richards, Jack S. [1 ,4 ,5 ]
Siba, Peter M. [9 ]
Fowkes, Freya J. I. [1 ,4 ,5 ,6 ,7 ]
Takashima, Eizo [10 ]
Tsuboi, Takafumi [10 ]
Mueller, Ivo [2 ,9 ,11 ]
Beeson, James G. [1 ,4 ,5 ,6 ,7 ]
机构：
[1] Burnet Inst, Melbourne, Vic 3004, Australia
[2] Inst Pasteur, F-75015 Paris, France
[3] Univ Adelaide, Sch Biol Sci, Res Ctr Infect Dis, Adelaide, SA 5005, Australia
[4] Univ Melbourne, Royal Melbourne Hosp, Dept Med, Melbourne, Vic 3010, Australia
[5] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia
[6] Monash Univ, Cent Clin Sch Infect Dis Immunol Epidemiol & Prev, Clayton, Vic 3800, Australia
[7] Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia
[8] Lund Univ, Skane Univ Hosp, Dept Lab Med, S-22185 Lund, Sweden
[9] Papua New Guinea Inst Med Res, Goroka, Ehp, Papua N Guinea
[10] Ehime Univ, Div Malaria Res, Proteosci Ctr, Matsuyama, Ehime 7908577, Japan
[11] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia
来源：
NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期
基金：
英国医学研究理事会; 美国国家卫生研究院; 澳大利亚国家健康与医学研究理事会;
关键词：
MEROZOITE SURFACE PROTEIN-2; PLASMODIUM-FALCIPARUM; INHIBITORY ANTIBODIES; GROWTH-INHIBITION; ANTIGENIC DIVERSITY; ACQUIRED-IMMUNITY; CLINICAL MALARIA; INVASION; VACCINE; ASSOCIATION;
D O I：
10.1038/s41467-019-08528-z
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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 antimalaria immune mechanisms, and identify specific merozoite antigens for further evaluation as vaccine candidates.
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页数：13
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