Antibodies to Intercellular Adhesion Molecule 1-Binding Plasmodium falciparum Erythrocyte Membrane Protein 1-DBLβ Are Biomarkers of Protective Immunity to Malaria in a Cohort of Young Children from Papua New Guinea

التفاصيل البيبلوغرافية
العنوان: Antibodies to Intercellular Adhesion Molecule 1-Binding Plasmodium falciparum Erythrocyte Membrane Protein 1-DBLβ Are Biomarkers of Protective Immunity to Malaria in a Cohort of Young Children from Papua New Guinea
المؤلفون: Diana S. Hansen, Andrew V. Oleinikov, Bent O. Petersen, Ivo Mueller, Clara S. Lin, Sofonias K. Tessema, Alyssa E. Barry, Livingstone Tavul, Dominic P. Kwiatkowski, Olga Chesnokov, Anthony N. Hodder, Jakob S. Jespersen, G. L. Abby Harrison, Thomas Lavstsen, Peter Siba, Digjaya Utama
المصدر: Tessema, S K, Utama, D, Chesnokov, O, Hodder, A N, Lin, C S, Harrison, G L A, Jespersen, J S, Petersen, B, Tavul, L, Siba, P, Kwiatkowski, D, Lavstsen, T, Hansen, D S, Oleinikov, A V, Mueller, I & Barry, A E 2018, ' Antibodies to Intercellular Adhesion Molecule 1-Binding Plasmodium falciparum Erythrocyte Membrane Protein 1-DBLβ Are Biomarkers of Protective Immunity to Malaria in a Cohort of Young Children from Papua New Guinea ', Infection and Immunity, vol. 86, no. 8, e00485-17 . https://doi.org/10.1128/IAI.00485-17
سنة النشر: 2017
مصطلحات موضوعية: 0301 basic medicine, Male, Protozoan Proteins, Antibodies, Protozoan, Group A, ICAM1, 0302 clinical medicine, Malaria, Falciparum, Phylogeny, Endothelial protein C receptor, Diversity, biology, Incidence, Endothelial Protein C Receptor, Intercellular Adhesion Molecule-1, Infectious Diseases, Cerebral Malaria, Child, Preschool, Microbial Immunity and Vaccines, Female, Antibody, Protein Binding, Immunology, Antigens, Protozoan, Microbiology, Risk Assessment, Antibodies, 03 medical and health sciences, EPCR, var genes, Papua New Guinea, Antigen, SDG 3 - Good Health and Well-being, Protein Domains, parasitic diseases, medicine, Antigenic variation, Humans, DBLβ, Genetic Variation, Infant, Plasmodium falciparum, medicine.disease, biology.organism_classification, Malaria, PfEMP1, 030104 developmental biology, biology.protein, Parasitology, Biomarkers, 030215 immunology, Follow-Up Studies
الوصف: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) mediates parasite sequestration to the cerebral microvasculature via binding of DBLβ domains to intercellular adhesion molecule 1 (ICAM1) and is associated with severe cerebral malaria. In a cohort of 187 young children from Papua New Guinea (PNG), we examined baseline levels of antibody to the ICAM1-binding PfEMP1 domain, DBLβ3PF11_0521, in comparison to four control antigens, including NTS-DBLα and CIDR1 domains from another group A variant and a group B/C variant. Antibody levels for the group A antigens were strongly associated with age and exposure. Antibody responses to DBLβ3PF11_0521 were associated with a 37% reduced risk of high-density clinical malaria in the follow-up period (adjusted incidence risk ratio [aIRR] = 0.63 [95% confidence interval {CI}, 0.45 to 0.88; P = 0.007]) and a 25% reduction in risk of low-density clinical malaria (aIRR = 0.75 [95% CI, 0.55 to 1.01; P = 0.06]), while there was no such association for other variants. Children who experienced severe malaria also had significantly lower levels of antibody to DBLβ3PF11_0521 and the other group A domains than those that experienced nonsevere malaria. Furthermore, a subset of PNG DBLβ sequences had ICAM1-binding motifs, formed a distinct phylogenetic cluster, and were similar to sequences from other areas of endemicity. PfEMP1 variants associated with these DBLβ domains were enriched for DC4 and DC13 head structures implicated in endothelial protein C receptor (EPCR) binding and severe malaria, suggesting conservation of dual binding specificities. These results provide further support for the development of specific classes of PfEMP1 as vaccine candidates and as biomarkers for protective immunity against clinical P. falciparum malaria.
وصف الملف: application/pdf
تدمد: 1098-5522
DOI: 10.1128/IAI.00485-17
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2c1c356d4f7c3382688021dc8494ad44
https://pubmed.ncbi.nlm.nih.gov/29784862
Rights: OPEN
رقم الانضمام: edsair.doi.dedup.....2c1c356d4f7c3382688021dc8494ad44
قاعدة البيانات: OpenAIRE
الوصف
تدمد:10985522
DOI:10.1128/IAI.00485-17