Antibody responses to the full-length VAR2CSA and its DBL domains in Cameroonian children and teenagers.
BACKGROUND
Antigenic variation of Plasmodium falciparum erythrocyte membrane protein 1 is a key parasite mechanism for immune evasion and parasite survival. It is assumed that the number of parasites expressing the same var gene must reach high enough numbers before the host can produce detectable levels of antibodies (Ab) to the variant. VAR2CSA is a protein coded for by one of 60 var genes that is expressed on the surface of infected erythrocytes (IE) and mediates IE binding to the placenta. The idea that Ab to VAR2CSA are pregnancy-associated was challenged when VAR2CSA-specific Ab were reported in children and men. However, the frequency and conditions under which Ab to VAR2CSA are produced outside pregnancy is unclear. This study sought to determine frequency, specificity and level of Ab to VAR2CSA produced in children and whether children with hyperparasitaemia and severe malaria are more likely to produce Ab to VAR2CSA compared to healthy children.


METHODS
Antibody responses to a panel of recombinant proteins consisting of multiple VAR2CSA Duffy-binding-like domains (DBL) and full-length VAR2CSA (FV2) were characterized in 193 1-15 year old children from rural Cameroonian villages and 160 children with severe malaria from the city.


RESULTS
Low Ab levels to VAR2CSA were detected in children; however, Ab levels to FV2 in teenagers were rare. Children preferentially recognized DBL2 (56-70%) and DBL4 (50-60%), while multigravidae produced high levels of IgG to DBL3, DBL5 and FV2. Sixty-seven percent of teenage girls (n = 16/24) recognized ID1-ID2a region of VAR2CSA. Children with severe forms of malaria had significantly higher IgG to merozoite antigens (all p < 0.05), but not to VAR2CSA (all p > 0.05) when compared to the healthy children.


CONCLUSIONS
The study suggests that children, including teenage girls acquire Ab to VAR2CSA domains and FV2, but Ab levels are much lower than those needed to protect women from placental infections and repertoire of Ab responses to DBL domains is different from those in pregnant women. Interestingly, children with severe malaria did not have higher Ab levels to VAR2CSA compared to healthy children.
Department of Biochemistry, Faculty of Medicine and Biomedical Research, Biotechnology Centre, University of Yaoundé 1, Yaounde, Cameroon. fodjoyetgang@gmail.com.
Barriere A Y
BA
Fodjo
Department of Biochemistry, Faculty of Medicine and Biomedical Research, Biotechnology Centre, University of Yaoundé 1, Yaounde, Cameroon.
Njika
N
Atemnkeng
Department of Biochemistry, Faculty of Medicine and Biomedical Research, Biotechnology Centre, University of Yaoundé 1, Yaounde, Cameroon.
Livo
L
Esemu
Department of Biochemistry, Faculty of Medicine and Biomedical Research, Biotechnology Centre, University of Yaoundé 1, Yaounde, Cameroon.
Emile K
EK
Yuosembom
School of Public Health, College of Health Sciences, University of Ghana, Legon, Ghana.
Isabella A
IA
Quakyi
Department of Biochemistry, Faculty of Medicine and Biomedical Research, Biotechnology Centre, University of Yaoundé 1, Yaounde, Cameroon.
Viviane H M
VH
Tchinda
Seattle Biomedical Research Institute, Seattle, WA, 98109, USA.
Joseph
J
Smith
Department of Immunology and Microbiology, Centre for Medical Parasitology, University of Copenhagen, Copenhagen, Denmark.
Ali
A
Salanti
Department of Biochemistry, Faculty of Medicine and Biomedical Research, Biotechnology Centre, University of Yaoundé 1, Yaounde, Cameroon.
Jude
J
Bigoga
Department of Tropical Medicine, Medical Microbiology and Pharmacology, University of Hawaii at Manoa, John A Burns School of Medicine, 651 Ilalo Street, BSB 320, Honolulu, Hawaii, 96813, USA.
Diane W
DW
Taylor
Department of Biochemistry, Faculty of Medicine and Biomedical Research, Biotechnology Centre, University of Yaoundé 1, Yaounde, Cameroon.
Rose G F
RG
Leke
Department of Tropical Medicine, Medical Microbiology and Pharmacology, University of Hawaii at Manoa, John A Burns School of Medicine, 651 Ilalo Street, BSB 320, Honolulu, Hawaii, 96813, USA.
Anna
A
Babakhanyan
D000293:Adolescent; D000913:Antibodies, Protozoan / Q000097:blood*; D000917:Antibody Formation; D000953:Antigens, Protozoan / Q000276:immunology*; D002163:Cameroon; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C512601:VAR2CSA protein, Plasmodium falciparum
Antibody; Children; Malaria; VAR2CSA