Human antibodies fix complement to inhibit Plasmodium falciparum invasion of erythrocytes and are associated with protection against malaria.
Immunity
; 42(3): 580-90, 2015 Mar 17.
Article
in En
| MEDLINE
| ID: mdl-25786180
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Plasmodium falciparum
/
Antibodies, Protozoan
/
Complement C1q
/
Malaria, Falciparum
/
Malaria Vaccines
/
Parasitemia
/
Merozoites
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Animals
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Language:
En
Journal:
Immunity
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2015
Document type:
Article
Affiliation country:
Australia
Country of publication:
United States