Association between naturally acquired antibodies to erythrocyte-binding antigens of Plasmodium falciparum and protection from malaria and high-density parasitemia

Clin Infect Dis. 2010 Oct 15;51(8):e50-60. doi: 10.1086/656413.


Background: Antibodies targeting blood stage antigens are important in protection against malaria, but the principle targets remain unclear. Erythrocyte-binding antigens (EBAs) are important erythrocyte invasion ligands used by merozoites and may be targets of protective immunity, but there are limited data examining their potential importance.

Methods: We examined antibodies among 206 Papua New Guinean children who were treated with antimalarials at enrollment and observed prospectively for 6 months for reinfection and malaria. Immunoglobulin (Ig) G, IgG subclasses, and IgM to different regions of EBA175, EBA140, and EBA181 expressed as recombinant proteins were assessed in comparison with several other merozoite antigens.

Results: High levels of IgG to each of the EBAs were strongly associated with protection from symptomatic malaria and high density parasitemia, but not with risk of reinfection per se. The predominant IgG subclasses were either IgG1 or IgG3, depending on the antigen. The predominance of IgG1 versus IgG3 reflected structural features of specific regions of the proteins. IgG3 was most strongly associated with protection, even for those antigens that had an IgG1 predominant response.

Conclusions: The EBAs appear important targets of acquired protective immunity. These findings support their further development as vaccine candidates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Protozoan / blood*
  • Antibodies, Protozoan / immunology*
  • Antigens, Protozoan / immunology*
  • Antimalarials / therapeutic use
  • Child
  • Child, Preschool
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / prevention & control*
  • Papua New Guinea
  • Parasitemia / drug therapy
  • Parasitemia / immunology*
  • Prospective Studies
  • Protozoan Proteins / immunology*
  • Receptors, Cell Surface / immunology*
  • Recombinant Proteins


  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Antimalarials
  • Duffy antigen binding protein, Plasmodium
  • Immunoglobulin G
  • Immunoglobulin M
  • Protozoan Proteins
  • Receptors, Cell Surface
  • Recombinant Proteins