Global Repertoire of Human Antibodies Against Plasmodium falciparum RIFINs, SURFINs, and STEVORs in a Malaria Exposed Population
Clinical immunity to malaria develops after repeated exposure to Plasmodium falciparum parasites. Broadly reactive antibodies against parasite antigens expressed on the surface of infected erythrocytes (variable surface antigens; VSAs) are candidates for anti-malaria therapeutics and vaccines. Among...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-05-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00893/full |
| _version_ | 1818499685534400512 |
|---|---|
| author | Bernard N. Kanoi Hikaru Nagaoka Michael T. White Masayuki Morita Nirianne M. Q. Palacpac Edward H. Ntege Betty Balikagala Adoke Yeka Thomas G. Egwang Toshihiro Horii Takafumi Tsuboi Eizo Takashima |
| author_facet | Bernard N. Kanoi Hikaru Nagaoka Michael T. White Masayuki Morita Nirianne M. Q. Palacpac Edward H. Ntege Betty Balikagala Adoke Yeka Thomas G. Egwang Toshihiro Horii Takafumi Tsuboi Eizo Takashima |
| author_sort | Bernard N. Kanoi |
| collection | DOAJ |
| description | Clinical immunity to malaria develops after repeated exposure to Plasmodium falciparum parasites. Broadly reactive antibodies against parasite antigens expressed on the surface of infected erythrocytes (variable surface antigens; VSAs) are candidates for anti-malaria therapeutics and vaccines. Among the VSAs, several RIFIN, STEVOR, and SURFIN family members have been demonstrated to be targets of naturally acquired immunity against malaria. For example, RIFIN family members are important ligands for opsonization of P. falciparum infected erythrocytes with specific immunoglobulins (IgG) acquiring broad protective reactivity. However, the global repertoire of human anti-VSAs IgG, its variation in children, and the key protective targets remain poorly understood. Here, we report wheat germ cell-free system-based production and serological profiling of a comprehensive library of A-RIFINs, B-RIFINs, STEVORs, and SURFINs derived from the P. falciparum 3D7 parasite strain. We observed that >98% of assayed proteins (n = 265) were immunogenic in malaria-exposed individuals in Uganda. The overall breadth of immune responses was significantly correlated with age but not with clinical malaria outcome among the study volunteers. However, children with high levels of antibodies to four RIFINs (PF3D7_0201000, PF3D7_1254500, PF3D7_1040600, PF3D7_1041100), STEVOR (PF3D7_0732000), and SURFIN 1.2 (PF3D7_0113600) had prospectively reduced the risk of developing febrile malaria, suggesting that the 5 antigens are important targets of protective immunity. Further studies on the significance of repeated exposure to malaria infection and maintenance of such high-level antibodies would contribute to a better understanding of susceptibility and naturally acquired immunity to malaria. |
| first_indexed | 2024-12-10T20:32:48Z |
| format | Article |
| id | doaj.art-c517a7da606b4040a3210528cce8dc71 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T20:32:48Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c517a7da606b4040a3210528cce8dc712022-12-22T01:34:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-05-011110.3389/fimmu.2020.00893525640Global Repertoire of Human Antibodies Against Plasmodium falciparum RIFINs, SURFINs, and STEVORs in a Malaria Exposed PopulationBernard N. Kanoi0Hikaru Nagaoka1Michael T. White2Masayuki Morita3Nirianne M. Q. Palacpac4Edward H. Ntege5Betty Balikagala6Adoke Yeka7Thomas G. Egwang8Toshihiro Horii9Takafumi Tsuboi10Eizo Takashima11Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, JapanDivision of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, JapanDepartment of Parasites and Insect Vectors, Pasteur Institute, Paris, FranceDivision of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, JapanDepartment of Malaria Vaccine Development, Research Institute for Microbial Diseases, Osaka University, Suita, JapanDepartment of Plastic and Reconstructive Surgery, Graduate School of Medicine and Hospital, University of the Ryukyus, Okinawa, JapanDepartment of Tropical Medicine and Parasitology, School of Medicine, Juntendo University, Tokyo, JapanMakerere University School of Public Health, Kampala, UgandaMed Biotech Laboratories, Kampala, UgandaDepartment of Malaria Vaccine Development, Research Institute for Microbial Diseases, Osaka University, Suita, JapanDivision of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, JapanDivision of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, JapanClinical immunity to malaria develops after repeated exposure to Plasmodium falciparum parasites. Broadly reactive antibodies against parasite antigens expressed on the surface of infected erythrocytes (variable surface antigens; VSAs) are candidates for anti-malaria therapeutics and vaccines. Among the VSAs, several RIFIN, STEVOR, and SURFIN family members have been demonstrated to be targets of naturally acquired immunity against malaria. For example, RIFIN family members are important ligands for opsonization of P. falciparum infected erythrocytes with specific immunoglobulins (IgG) acquiring broad protective reactivity. However, the global repertoire of human anti-VSAs IgG, its variation in children, and the key protective targets remain poorly understood. Here, we report wheat germ cell-free system-based production and serological profiling of a comprehensive library of A-RIFINs, B-RIFINs, STEVORs, and SURFINs derived from the P. falciparum 3D7 parasite strain. We observed that >98% of assayed proteins (n = 265) were immunogenic in malaria-exposed individuals in Uganda. The overall breadth of immune responses was significantly correlated with age but not with clinical malaria outcome among the study volunteers. However, children with high levels of antibodies to four RIFINs (PF3D7_0201000, PF3D7_1254500, PF3D7_1040600, PF3D7_1041100), STEVOR (PF3D7_0732000), and SURFIN 1.2 (PF3D7_0113600) had prospectively reduced the risk of developing febrile malaria, suggesting that the 5 antigens are important targets of protective immunity. Further studies on the significance of repeated exposure to malaria infection and maintenance of such high-level antibodies would contribute to a better understanding of susceptibility and naturally acquired immunity to malaria.https://www.frontiersin.org/article/10.3389/fimmu.2020.00893/fullPlasmodium falciparumRIFINSTEVORSURFINnaturally acquired immunity |
| spellingShingle | Bernard N. Kanoi Hikaru Nagaoka Michael T. White Masayuki Morita Nirianne M. Q. Palacpac Edward H. Ntege Betty Balikagala Adoke Yeka Thomas G. Egwang Toshihiro Horii Takafumi Tsuboi Eizo Takashima Global Repertoire of Human Antibodies Against Plasmodium falciparum RIFINs, SURFINs, and STEVORs in a Malaria Exposed Population Frontiers in Immunology Plasmodium falciparum RIFIN STEVOR SURFIN naturally acquired immunity |
| title | Global Repertoire of Human Antibodies Against Plasmodium falciparum RIFINs, SURFINs, and STEVORs in a Malaria Exposed Population |
| title_full | Global Repertoire of Human Antibodies Against Plasmodium falciparum RIFINs, SURFINs, and STEVORs in a Malaria Exposed Population |
| title_fullStr | Global Repertoire of Human Antibodies Against Plasmodium falciparum RIFINs, SURFINs, and STEVORs in a Malaria Exposed Population |
| title_full_unstemmed | Global Repertoire of Human Antibodies Against Plasmodium falciparum RIFINs, SURFINs, and STEVORs in a Malaria Exposed Population |
| title_short | Global Repertoire of Human Antibodies Against Plasmodium falciparum RIFINs, SURFINs, and STEVORs in a Malaria Exposed Population |
| title_sort | global repertoire of human antibodies against plasmodium falciparum rifins surfins and stevors in a malaria exposed population |
| topic | Plasmodium falciparum RIFIN STEVOR SURFIN naturally acquired immunity |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00893/full |
| work_keys_str_mv | AT bernardnkanoi globalrepertoireofhumanantibodiesagainstplasmodiumfalciparumrifinssurfinsandstevorsinamalariaexposedpopulation AT hikarunagaoka globalrepertoireofhumanantibodiesagainstplasmodiumfalciparumrifinssurfinsandstevorsinamalariaexposedpopulation AT michaeltwhite globalrepertoireofhumanantibodiesagainstplasmodiumfalciparumrifinssurfinsandstevorsinamalariaexposedpopulation AT masayukimorita globalrepertoireofhumanantibodiesagainstplasmodiumfalciparumrifinssurfinsandstevorsinamalariaexposedpopulation AT niriannemqpalacpac globalrepertoireofhumanantibodiesagainstplasmodiumfalciparumrifinssurfinsandstevorsinamalariaexposedpopulation AT edwardhntege globalrepertoireofhumanantibodiesagainstplasmodiumfalciparumrifinssurfinsandstevorsinamalariaexposedpopulation AT bettybalikagala globalrepertoireofhumanantibodiesagainstplasmodiumfalciparumrifinssurfinsandstevorsinamalariaexposedpopulation AT adokeyeka globalrepertoireofhumanantibodiesagainstplasmodiumfalciparumrifinssurfinsandstevorsinamalariaexposedpopulation AT thomasgegwang globalrepertoireofhumanantibodiesagainstplasmodiumfalciparumrifinssurfinsandstevorsinamalariaexposedpopulation AT toshihirohorii globalrepertoireofhumanantibodiesagainstplasmodiumfalciparumrifinssurfinsandstevorsinamalariaexposedpopulation AT takafumitsuboi globalrepertoireofhumanantibodiesagainstplasmodiumfalciparumrifinssurfinsandstevorsinamalariaexposedpopulation AT eizotakashima globalrepertoireofhumanantibodiesagainstplasmodiumfalciparumrifinssurfinsandstevorsinamalariaexposedpopulation |