The antibody response of pregnant Cameroonian women to VAR2CSA ID1-ID2a, a small recombinant protein containing the CSA-binding site

• Published in: PloS one 2014-02, Vol.9 (2), p.e88173-e88173
• Main Authors: Babakhanyan, Anna, Leke, Rose G F, Salanti, Ali, Bobbili, Naveen, Gwanmesia, Philomina, Leke, Robert J I, Quakyi, Isabella A, Chen, John J, Taylor, Diane Wallace
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anemia; Antibodies; Antibodies, Protozoan - blood; Antibodies, Protozoan - immunology; Antibody Formation - immunology; Antibody response; Antigens; Antigens, Protozoan - immunology; Avidity; Binding sites; Binding Sites - immunology; Biology; Biomedical research; Biotechnology; Birth weight; Cameroon; Chondroitin sulfate; Committees; Cross Reactions - immunology; Cross-reactivity; Epitopes; Epitopes - immunology; Erythrocytes; Erythrocytes - immunology; Erythrocytes - parasitology; Female; Humans; Immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunoglobulin M; Immunoglobulin M - blood; Immunoglobulin M - immunology; Immunoglobulins; Malaria; Malaria, Falciparum - immunology; Male; Males; Medicine; Men; Pharmacology; Placenta; Placenta - immunology; Placenta - parasitology; Plasmodium falciparum; Plasmodium falciparum - immunology; Pregnancy; Pregnancy Complications, Parasitic - blood; Pregnancy Complications, Parasitic - immunology; Pregnancy Complications, Parasitic - parasitology; Pregnant women; Protein binding; Proteins; Recombinant proteins; Recombinant Proteins - immunology; Studies; Sulfates; Vaccination; Vector-borne diseases; Womens health; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0088173

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.