Association between naturally acquired antibodies to erythrocyte-binding antigens of Plasmodium falciparum and protection from malaria and high-density parasitemia.
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.
Richards
Jack S
JS
Department of Medical Biology, Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Victoria, Australia.
Stanisic
Danielle I
DI
Fowkes
Freya J I
FJ
Tavul
Livingstone
L
Dabod
Elijah
E
Thompson
Jennifer K
JK
Kumar
Sanjeev
S
Chitnis
Chetan E
CE
Narum
David L
DL
Michon
Pascal
P
Siba
Peter M
PM
Cowman
Alan F
AF
Mueller
Ivo
I
Beeson
James G
JG
D000293:Adolescent; D000913:Antibodies, Protozoan / Q000097:blood* / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology*; D000962:Antimalarials / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control*; D010219:Papua New Guinea; D018512:Parasitemia / Q000188:drug therapy / Q000276:immunology*; D011446:Prospective Studies; D015800:Protozoan Proteins / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D011994:Recombinant Proteins
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000962:Antimalarials; C066001:Duffy antigen binding protein, Plasmodium; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins