期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-08528-z
关键词
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资金
- National Health and Medical Research Council of Australia [1092789, 1077636]
- International Centers for Excellence in Malaria Research of the National Institutes of Health [5U19AI129392]
- JSPS KAKENHI in Japan [JP26253026]
- NHMRC Independent Research Institutes Support Scheme
- Operational Infrastructure Support of the Victorian State Government
- National Health and Medical Research Council of Australia [1077636] Funding Source: NHMRC
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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