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Human antibodies fix complement to inhibit Plasmodium falciparum invasion of erythrocytes and are associated with protection against malaria.

Abstract：

:Antibodies play major roles in immunity to malaria; however, a limited understanding of mechanisms mediating protection is a major barrier to vaccine development. We have demonstrated that acquired human anti-malarial antibodies promote complement deposition on the merozoite to mediate inhibition of erythrocyte invasion through C1q fixation and activation of the classical complement pathway. Antibody-mediated complement-dependent (Ab-C') inhibition was the predominant invasion-inhibitory activity of human antibodies; most antibodies were non-inhibitory without complement. Inhibitory activity was mediated predominately via C1q fixation, and merozoite surface proteins 1 and 2 were identified as major targets. Complement fixation by antibodies was very strongly associated with protection from both clinical malaria and high-density parasitemia in a prospective longitudinal study of children. Ab-C' inhibitory activity could be induced by human immunization with a candidate merozoite surface-protein vaccine. Our findings demonstrate that human anti-malarial antibodies have evolved to function by fixing complement for potent invasion-inhibitory activity and protective immunity.

journal_name

Immunity

journal_title

Immunity

authors

Boyle MJ,Reiling L,Feng G,Langer C,Osier FH,Aspeling-Jones H,Cheng YS,Stubbs J,Tetteh KK,Conway DJ,McCarthy JS,Muller I,Marsh K,Anders RF,Beeson JG

doi

10.1016/j.immuni.2015.02.012

subject

Has Abstract

pub_date

2015-03-17 00:00:00

pages

580-90

issue

3

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(15)00087-4

journal_volume

42

pub_type

临床试验,杂志文章

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