The acquisition of humoral immune responses targeting Plasmodium falciparum sexual stages in controlled human malaria infections
Individuals infected with P. falciparum develop antibody responses to intra-erythrocytic gametocyte proteins and exported gametocyte proteins present on the surface of infected erythrocytes. However, there is currently limited knowledge on the immunogenicity of gametocyte antigens and the specificit...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.930956/full |
| _version_ | 1818097132601606144 |
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| author | Roos M. de Jong Manon Alkema Tate Oulton Elin Dumont Karina Teelen Rie Nakajima Rafael Ramiro de Assis Kathleen W. Dantzler Press Priscilla Ngotho Kevin K.A. Tetteh Phil Felgner Matthias Marti Katharine A. Collins Chris Drakeley Teun Bousema Teun Bousema Will J.R. Stone |
| author_facet | Roos M. de Jong Manon Alkema Tate Oulton Elin Dumont Karina Teelen Rie Nakajima Rafael Ramiro de Assis Kathleen W. Dantzler Press Priscilla Ngotho Kevin K.A. Tetteh Phil Felgner Matthias Marti Katharine A. Collins Chris Drakeley Teun Bousema Teun Bousema Will J.R. Stone |
| author_sort | Roos M. de Jong |
| collection | DOAJ |
| description | Individuals infected with P. falciparum develop antibody responses to intra-erythrocytic gametocyte proteins and exported gametocyte proteins present on the surface of infected erythrocytes. However, there is currently limited knowledge on the immunogenicity of gametocyte antigens and the specificity of gametocyte-induced antibody responses. In this study, we assessed antibody responses in participants of two controlled human malaria infection (CHMI) studies by ELISA, multiplexed bead-based antibody assays and protein microarray. By comparing antibody responses in participants with and without gametocyte exposure, we aimed to disentangle the antibody response induced by asexual and sexual stage parasites. We showed that after a single malaria infection, a significant anti-sexual stage humoral response is induced in malaria-naïve individuals, even after exposure to relatively low gametocyte densities (up to ~1,600 gametocytes/mL). In contrast to antibody responses to well-characterised asexual blood stage antigens that were detectable by day 21 after infection, responses to sexual stage antigens (including transmission blocking vaccine candidates Pfs48/45 and Pfs230) were only apparent at 51 days after infection. We found antigens previously associated with early gametocyte or anti-gamete immunity were highly represented among responses linked with gametocyte exposure. Our data provide detailed insights on the induction and kinetics of antibody responses to gametocytes and identify novel antigens that elicit antibody responses exclusively in individuals with gametocyte exposure. Our findings provide target identification for serological assays for surveillance of the malaria infectious reservoir, and support vaccine development by describing the antibody response to leading vaccine antigens after primary infection. |
| first_indexed | 2024-12-10T23:15:40Z |
| format | Article |
| id | doaj.art-c3be23fae6034f06b4d6262882e0d66d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T23:15:40Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c3be23fae6034f06b4d6262882e0d66d2022-12-22T01:29:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.930956930956The acquisition of humoral immune responses targeting Plasmodium falciparum sexual stages in controlled human malaria infectionsRoos M. de Jong0Manon Alkema1Tate Oulton2Elin Dumont3Karina Teelen4Rie Nakajima5Rafael Ramiro de Assis6Kathleen W. Dantzler Press7Priscilla Ngotho8Kevin K.A. Tetteh9Phil Felgner10Matthias Marti11Katharine A. Collins12Chris Drakeley13Teun Bousema14Teun Bousema15Will J.R. Stone16Department of Medical Microbiology and Radboud Centre of Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Medical Microbiology and Radboud Centre of Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United KingdomDepartment of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United KingdomDepartment of Medical Microbiology and Radboud Centre of Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, United StatesDepartment of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, United StatesDepartment of Medicine, Stanford University, Stanford, CA, United StatesWellcome Centre for Integrative Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United KingdomDepartment of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United KingdomDepartment of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, United StatesWellcome Centre for Integrative Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United KingdomDepartment of Medical Microbiology and Radboud Centre of Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United KingdomDepartment of Medical Microbiology and Radboud Centre of Infectious Diseases, Radboud University Medical Centre, Nijmegen, NetherlandsDepartment of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United KingdomDepartment of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United KingdomIndividuals infected with P. falciparum develop antibody responses to intra-erythrocytic gametocyte proteins and exported gametocyte proteins present on the surface of infected erythrocytes. However, there is currently limited knowledge on the immunogenicity of gametocyte antigens and the specificity of gametocyte-induced antibody responses. In this study, we assessed antibody responses in participants of two controlled human malaria infection (CHMI) studies by ELISA, multiplexed bead-based antibody assays and protein microarray. By comparing antibody responses in participants with and without gametocyte exposure, we aimed to disentangle the antibody response induced by asexual and sexual stage parasites. We showed that after a single malaria infection, a significant anti-sexual stage humoral response is induced in malaria-naïve individuals, even after exposure to relatively low gametocyte densities (up to ~1,600 gametocytes/mL). In contrast to antibody responses to well-characterised asexual blood stage antigens that were detectable by day 21 after infection, responses to sexual stage antigens (including transmission blocking vaccine candidates Pfs48/45 and Pfs230) were only apparent at 51 days after infection. We found antigens previously associated with early gametocyte or anti-gamete immunity were highly represented among responses linked with gametocyte exposure. Our data provide detailed insights on the induction and kinetics of antibody responses to gametocytes and identify novel antigens that elicit antibody responses exclusively in individuals with gametocyte exposure. Our findings provide target identification for serological assays for surveillance of the malaria infectious reservoir, and support vaccine development by describing the antibody response to leading vaccine antigens after primary infection.https://www.frontiersin.org/articles/10.3389/fimmu.2022.930956/fullmalariaPlasmodium falciparumsexual stagegametocyte antigensantibody responsescontrolled human malaria infection (CHMI) |
| spellingShingle | Roos M. de Jong Manon Alkema Tate Oulton Elin Dumont Karina Teelen Rie Nakajima Rafael Ramiro de Assis Kathleen W. Dantzler Press Priscilla Ngotho Kevin K.A. Tetteh Phil Felgner Matthias Marti Katharine A. Collins Chris Drakeley Teun Bousema Teun Bousema Will J.R. Stone The acquisition of humoral immune responses targeting Plasmodium falciparum sexual stages in controlled human malaria infections Frontiers in Immunology malaria Plasmodium falciparum sexual stage gametocyte antigens antibody responses controlled human malaria infection (CHMI) |
| title | The acquisition of humoral immune responses targeting Plasmodium falciparum sexual stages in controlled human malaria infections |
| title_full | The acquisition of humoral immune responses targeting Plasmodium falciparum sexual stages in controlled human malaria infections |
| title_fullStr | The acquisition of humoral immune responses targeting Plasmodium falciparum sexual stages in controlled human malaria infections |
| title_full_unstemmed | The acquisition of humoral immune responses targeting Plasmodium falciparum sexual stages in controlled human malaria infections |
| title_short | The acquisition of humoral immune responses targeting Plasmodium falciparum sexual stages in controlled human malaria infections |
| title_sort | acquisition of humoral immune responses targeting plasmodium falciparum sexual stages in controlled human malaria infections |
| topic | malaria Plasmodium falciparum sexual stage gametocyte antigens antibody responses controlled human malaria infection (CHMI) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.930956/full |
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