Differential recognition of terminal extracellular Plasmodium falciparum VAR2CSA domains by sera from multigravid, malaria-exposed Malian women.
The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family mediates parasite sequestration in small capillaries through tissue-specific cytoadherence. The best characterized of these proteins is VAR2CSA, which is expressed on the surface of infected erythrocytes that bind to chondroitin sulfate in the placental matrix. Antibodies to VAR2CSA prevent placental cytoadherence and protect against placental malaria. The size and complexity of the VAR2CSA protein pose challenges for vaccine development, but smaller constitutive domains may be suitable for subunit vaccine development. A protein microarray was printed to include five overlapping fragments of the 3D7 VAR2CSA extracellular region. Malian women with a history of at least one pregnancy had antibody recognition of four of these fragments and had stronger reactivity against the two distal fragments than did nulliparous women, children, and men from Mali, suggesting that the C-terminal extracellular VAR2CSA domains are a potential focus of protective immunity. With carefully chosen sera from longitudinal studies of pregnant women, this approach has the potential to identify seroreactive VAR2CSA domains associated with protective immunity against pregnancy-associated malaria.
Mark A
MA
Travassos
Drissa
D
Coulibaly
Jason A
JA
Bailey
Amadou
A
Niangaly
Matthew
M
Adams
Myaing M
MM
Nyunt
Amed
A
Ouattara
Kirsten E
KE
Lyke
Matthew B
MB
Laurens
Jozelyn
J
Pablo
Algis
A
Jasinskas
Rie
R
Nakajima
Andrea A
AA
Berry
Shannon
S
Takala-Harrison
Abdoulaye K
AK
Kone
Bourema
B
Kouriba
J Alexandra
JA
Rowe
Ogobara K
OK
Doumbo
Mahamadou A
MA
Thera
Miriam K
MK
Laufer
Philip L
PL
Felgner
Christopher V
CV
Plowe
D000328:Adult; D000953:Antigens, Protozoan / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions / Q000276:immunology; D005260:Female; D020073:Gravidity / Q000276:immunology; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000276:immunology*; D008297:Male; D008302:Mali / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000276:immunology; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology*; D040081:Protein Array Analysis; D055815:Young Adult
D000953:Antigens, Protozoan; C512601:VAR2CSA protein, Plasmodium falciparum