Characterization of naturally acquired immunity to a panel of antigens expressed in mature P. falciparum gametocytes
<br><strong>Introduction: </strong>Naturally acquired immune responses against antigens expressed on the surface of mature gametocytes develop in individuals living in malaria-endemic areas. Evidence suggests that such anti-gametocyte immunity can block the development of the paras...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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Frontiers Media
2021
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| _version_ | 1826280155499200512 |
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| author | Muthui, MK Takashima, E Omondi, BR Marsh, K Bejon, P Kapulu, M |
| author_facet | Muthui, MK Takashima, E Omondi, BR Marsh, K Bejon, P Kapulu, M |
| author_sort | Muthui, MK |
| collection | OXFORD |
| description | <br><strong>Introduction: </strong>Naturally acquired immune responses against antigens expressed on the surface of mature gametocytes develop in individuals living in malaria-endemic areas. Evidence suggests that such anti-gametocyte immunity can block the development of the parasite in the mosquito, thus playing a role in interrupting transmission. A better comprehension of naturally acquired immunity to these gametocyte antigens can aid the development of transmission-blocking vaccines and improve our understanding of the human infectious reservoir.
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Methods: </strong>Antigens expressed on the surface of mature gametocytes that had not previously been widely studied for evidence of naturally acquired immunity were identified for protein expression alongside Pfs230-C using either the mammalian HEK293E or the wheat germ cell-free expression systems. Where there was sequence variation in the candidate antigens (3D7 vs a clinical isolate PfKE04), both variants were expressed. ELISA was used to assess antibody responses against these antigens, as well as against crude stage V gametocyte extract (GE) and AMA1 using archived plasma samples from individuals recruited to participate in malaria cohort studies. We analyzed antibody levels (estimated from optical density units using a standardized ELISA) and seroprevalence (defined as antibody levels greater than three standard deviations above the mean levels of a pool of malaria naïve sera). We described the dynamics of antibody responses to these antigens by identifying factors predictive of antibody levels using linear regression models.
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Results: </strong>Of the 25 antigens selected, seven antigens were produced successfully as recombinant proteins, with one variant antigen, giving a total of eight proteins for evaluation. Antibodies to the candidate antigens were detectable in the study population (N = 216), with seroprevalence ranging from 37.0% (95% CI: 30.6%, 43.9%) for PSOP1 to 77.8% (95% CI: 71.6%, 83.1%) for G377 (3D7 variant). Responses to AMA1 and GE were more prevalent than those to the gametocyte proteins at 87.9% (95% CI: 82.8%, 91.9%) and 88.3% (95% CI: 83.1%, 92.4%), respectively. Additionally, both antibody levels and breadth of antibody responses were associated with age and concurrent parasitaemia.
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Conclusion: </strong>Age and concurrent parasitaemia remain important determinants of naturally acquired immunity to gametocyte antigens. Furthermore, we identify novel candidates for transmission-blocking activity evaluation. |
| first_indexed | 2024-03-07T00:09:28Z |
| format | Journal article |
| id | oxford-uuid:78b66a8c-11d5-4e13-8481-35ff87d90a8e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:09:28Z |
| publishDate | 2021 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:78b66a8c-11d5-4e13-8481-35ff87d90a8e2022-03-26T20:32:32ZCharacterization of naturally acquired immunity to a panel of antigens expressed in mature P. falciparum gametocytesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:78b66a8c-11d5-4e13-8481-35ff87d90a8eEnglishSymplectic ElementsFrontiers Media2021Muthui, MKTakashima, EOmondi, BRMarsh, KBejon, PKapulu, M<br><strong>Introduction: </strong>Naturally acquired immune responses against antigens expressed on the surface of mature gametocytes develop in individuals living in malaria-endemic areas. Evidence suggests that such anti-gametocyte immunity can block the development of the parasite in the mosquito, thus playing a role in interrupting transmission. A better comprehension of naturally acquired immunity to these gametocyte antigens can aid the development of transmission-blocking vaccines and improve our understanding of the human infectious reservoir. <br><strong> Methods: </strong>Antigens expressed on the surface of mature gametocytes that had not previously been widely studied for evidence of naturally acquired immunity were identified for protein expression alongside Pfs230-C using either the mammalian HEK293E or the wheat germ cell-free expression systems. Where there was sequence variation in the candidate antigens (3D7 vs a clinical isolate PfKE04), both variants were expressed. ELISA was used to assess antibody responses against these antigens, as well as against crude stage V gametocyte extract (GE) and AMA1 using archived plasma samples from individuals recruited to participate in malaria cohort studies. We analyzed antibody levels (estimated from optical density units using a standardized ELISA) and seroprevalence (defined as antibody levels greater than three standard deviations above the mean levels of a pool of malaria naïve sera). We described the dynamics of antibody responses to these antigens by identifying factors predictive of antibody levels using linear regression models. <br><strong> Results: </strong>Of the 25 antigens selected, seven antigens were produced successfully as recombinant proteins, with one variant antigen, giving a total of eight proteins for evaluation. Antibodies to the candidate antigens were detectable in the study population (N = 216), with seroprevalence ranging from 37.0% (95% CI: 30.6%, 43.9%) for PSOP1 to 77.8% (95% CI: 71.6%, 83.1%) for G377 (3D7 variant). Responses to AMA1 and GE were more prevalent than those to the gametocyte proteins at 87.9% (95% CI: 82.8%, 91.9%) and 88.3% (95% CI: 83.1%, 92.4%), respectively. Additionally, both antibody levels and breadth of antibody responses were associated with age and concurrent parasitaemia. <br><strong> Conclusion: </strong>Age and concurrent parasitaemia remain important determinants of naturally acquired immunity to gametocyte antigens. Furthermore, we identify novel candidates for transmission-blocking activity evaluation. |
| spellingShingle | Muthui, MK Takashima, E Omondi, BR Marsh, K Bejon, P Kapulu, M Characterization of naturally acquired immunity to a panel of antigens expressed in mature P. falciparum gametocytes |
| title | Characterization of naturally acquired immunity to a panel of antigens expressed in mature P. falciparum gametocytes |
| title_full | Characterization of naturally acquired immunity to a panel of antigens expressed in mature P. falciparum gametocytes |
| title_fullStr | Characterization of naturally acquired immunity to a panel of antigens expressed in mature P. falciparum gametocytes |
| title_full_unstemmed | Characterization of naturally acquired immunity to a panel of antigens expressed in mature P. falciparum gametocytes |
| title_short | Characterization of naturally acquired immunity to a panel of antigens expressed in mature P. falciparum gametocytes |
| title_sort | characterization of naturally acquired immunity to a panel of antigens expressed in mature p falciparum gametocytes |
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