title: The antibody response of pregnant Cameroonian women to VAR2CSA ID1-ID2a, a small recombinant protein containing the CSA-binding site.
abstract: In pregnant women, Plasmodium falciparum-infected erythrocytes expressing the VAR2CSA antigen bind to chondroitin sulfate A in the placenta causing placental malaria. The binding site of VAR2CSA is present in the ID1-ID2a region. This study sought to determine if pregnant Cameroonian women naturally acquire antibodies to ID1-ID2a and if antibodies to ID1-ID2a correlate with absence of placental malaria at delivery. Antibody levels to full-length VAR2CSA and ID1-ID2a were measured in plasma samples from 745 pregnant Cameroonian women, 144 Cameroonian men, and 66 US subjects. IgM levels and IgG avidity to ID1-ID2a were also determined. As expected, antibodies to ID1-ID2a were absent in US controls. Although pregnant Cameroonian women developed increasing levels of antibodies to full-length VAR2CSA during pregnancy, no increase in either IgM or IgG to ID1-ID2a was observed. Surprisingly, no differences in antibody levels to ID1-ID2a were detected between Cameroonian men and pregnant women. For example, in rural settings only 8-9% of males had antibodies to full-length VAR2CSA, but 90-96% had antibodies to ID1-ID2a. In addition, no significant difference in the avidity of IgG to ID1-ID2a was found between pregnant women and Cameroonian men, and no correlation between antibody levels at delivery and absence of placental malaria was found. Thus, the response to ID1-ID2a was not pregnancy specific, but predominantly against cross-reactivity epitopes, which may have been induced by other PfEMP1 antigens, malarial antigens, or microbes. Currently, ID1-ID2a is a leading vaccine candidate, since it binds to the CSA with the same affinity as the full-length molecule and elicits binding-inhibitory antibodies in animals. Further studies are needed to determine if the presence of naturally acquired cross-reactive antibodies in women living in malaria endemic countries will alter the response to ID1-ID2a following vaccination with ID1-ID2a.
authors: Department of Tropical Medicine, Medical Microbiology and Pharmacology, University of Hawai'i at Manoa, John A. Burns School of Medicine, Honolulu, Hawai'i, United States of America.
authors: Anna
authors: A
authors: Babakhanyan
authors: The Biotechnology Center, Faculty of Medicine and Biomedical Research, University of Yaoundé 1, Yaoundé, Cameroon.
authors: Rose G F
authors: RG
authors: Leke
authors: Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors: Ali
authors: A
authors: Salanti
authors: Department of Tropical Medicine, Medical Microbiology and Pharmacology, University of Hawai'i at Manoa, John A. Burns School of Medicine, Honolulu, Hawai'i, United States of America.
authors: Naveen
authors: N
authors: Bobbili
authors: The Biotechnology Center, Faculty of Medicine and Biomedical Research, University of Yaoundé 1, Yaoundé, Cameroon.
authors: Philomina
authors: P
authors: Gwanmesia
authors: The Biotechnology Center, Faculty of Medicine and Biomedical Research, University of Yaoundé 1, Yaoundé, Cameroon.
authors: Robert J I
authors: RJ
authors: Leke
authors: School of Public Health, College of Health Sciences, University of Ghana, Legon, Ghana.
authors: Isabella A
authors: IA
authors: Quakyi
authors: Department of Tropical Medicine, Medical Microbiology and Pharmacology, University of Hawai'i at Manoa, John A. Burns School of Medicine, Honolulu, Hawai'i, United States of America.
authors: John J
authors: JJ
authors: Chen
authors: Department of Tropical Medicine, Medical Microbiology and Pharmacology, University of Hawai'i at Manoa, John A. Burns School of Medicine, Honolulu, Hawai'i, United States of America.
authors: Diane Wallace
authors: DW
authors: Taylor
mesh_terms: D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology*; D001665:Binding Sites / Q000276:immunology; D002163:Cameroon; D003429:Cross Reactions / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology; D008297:Male; D010920:Placenta / Q000276:immunology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D011994:Recombinant Proteins / Q000276:immunology*; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011994:Recombinant Proteins; C512601:VAR2CSA protein, Plasmodium falciparum