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Impact of the parasitic helminth Schistosoma mansoni on host anti-viral vaccine responses: proof of concept from the anti-polio vaccine
Schistosomiasis is a devastating and neglected tropical disease caused by Schistosoma spp. parasites. The disease remains greatly neglected by global health control programmes thus classified as a top neglected tropical disease of humankind. One of the most common species of these parasites, Schisto...
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| Language: | English |
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Department of Pathology
2022
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| _version_ | 1867613239775330304 |
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| access_status_str | Open Access |
| author | Musaigwa, Fungai |
| author2 | Nono, Komguep Justin |
| author_browse | Musaigwa, Fungai Nono, Komguep Justin |
| author_facet | Nono, Komguep Justin Musaigwa, Fungai |
| author_sort | Musaigwa, Fungai |
| collection | Thesis |
| description | Schistosomiasis is a devastating and neglected tropical disease caused by Schistosoma spp. parasites. The disease remains greatly neglected by global health control programmes thus classified as a top neglected tropical disease of humankind. One of the most common species of these parasites, Schistosoma mansoni, causes hepatosplenic schistosomiasis and distributes widely in sub-Saharan Africa. Schistosoma mansoni is physiologically debilitating and potentially deadly with a known potential as a master regulator of the host immune responses. However, the mechanistic bases and the scope of this immunoregulatory potential of S. mansoni still remain poorly understood. This study explored the influence of S. mansoni-driven schistosomiasis on vaccine-induced memory immunity in schoolchildren from a rural endemic area of Cameroon and in laboratory mice. As a proof of concept, a well-established anti-viral vaccination programme with wide global coverage, i.e., anti-polio vaccination, was evaluated for its sustainability in the face of schistosomiasis in human and mouse hosts. Our findings using the poliovirus specific enzyme-linked immunosorbent assay revealed a schistosomiasis-associated impairment of polio specific serologic antibody memory responses in previously vaccinated schoolchildren and mice, as judged by significantly reduced serum anti-polio IgG antibody levels. To explore our findings further, cellular evaluations were conducted using flow cytometry in mouse modes of vaccination and schistosomiasis. The reduction of anti-polio elicited antibody responses was paralleled by the general depletion, through reduced survival and increased cell death, of bone marrow plasma cells and plasma blasts in schistosomiasis-diseased mice. Notably, schistosomiasis reduced memory T cell responses as well in vaccinated hosts and considerably impaired the expression of survival markers on antibody-producing long term plasma cells in the bone marrow. When attempting to control the disease by administration of the sole commercially available drug for schistosomiasis control, praziquantel, the parasite-driven depletion of the plasma cell and memory T cell compartment was restored followed by a partial recovery of antibody-producing abilities in vaccinated hosts. Taken together, our findings unprecedentedly demonstrate how schistosomiasis might negatively influence the efficacy and potentially the effectiveness of anti-viral vaccine memory immunity. Additionally, we present findings on how strategic therapeutic interventions against schistosomiasis might positively influence vaccine-elicited anti-viral immunity in schistosomiasis-diseased hosts. Our results have robust implications for future more informed deployment of effective vaccination campaigns, beyond the sole consideration of coverage and encourage frequent mass drug administration of praziquantel in schistosomiasis-endemic areas to ensure the sustainability of vaccine elicited responses thus protection of the hosts against vaccine preventable diseases. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/36701 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:32:58.612Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| publisher | Department of Pathology |
| publisherStr | Department of Pathology |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/36701 Impact of the parasitic helminth Schistosoma mansoni on host anti-viral vaccine responses: proof of concept from the anti-polio vaccine Musaigwa, Fungai Nono, Komguep Justin Brombacher, Frank pathology Schistosomiasis is a devastating and neglected tropical disease caused by Schistosoma spp. parasites. The disease remains greatly neglected by global health control programmes thus classified as a top neglected tropical disease of humankind. One of the most common species of these parasites, Schistosoma mansoni, causes hepatosplenic schistosomiasis and distributes widely in sub-Saharan Africa. Schistosoma mansoni is physiologically debilitating and potentially deadly with a known potential as a master regulator of the host immune responses. However, the mechanistic bases and the scope of this immunoregulatory potential of S. mansoni still remain poorly understood. This study explored the influence of S. mansoni-driven schistosomiasis on vaccine-induced memory immunity in schoolchildren from a rural endemic area of Cameroon and in laboratory mice. As a proof of concept, a well-established anti-viral vaccination programme with wide global coverage, i.e., anti-polio vaccination, was evaluated for its sustainability in the face of schistosomiasis in human and mouse hosts. Our findings using the poliovirus specific enzyme-linked immunosorbent assay revealed a schistosomiasis-associated impairment of polio specific serologic antibody memory responses in previously vaccinated schoolchildren and mice, as judged by significantly reduced serum anti-polio IgG antibody levels. To explore our findings further, cellular evaluations were conducted using flow cytometry in mouse modes of vaccination and schistosomiasis. The reduction of anti-polio elicited antibody responses was paralleled by the general depletion, through reduced survival and increased cell death, of bone marrow plasma cells and plasma blasts in schistosomiasis-diseased mice. Notably, schistosomiasis reduced memory T cell responses as well in vaccinated hosts and considerably impaired the expression of survival markers on antibody-producing long term plasma cells in the bone marrow. When attempting to control the disease by administration of the sole commercially available drug for schistosomiasis control, praziquantel, the parasite-driven depletion of the plasma cell and memory T cell compartment was restored followed by a partial recovery of antibody-producing abilities in vaccinated hosts. Taken together, our findings unprecedentedly demonstrate how schistosomiasis might negatively influence the efficacy and potentially the effectiveness of anti-viral vaccine memory immunity. Additionally, we present findings on how strategic therapeutic interventions against schistosomiasis might positively influence vaccine-elicited anti-viral immunity in schistosomiasis-diseased hosts. Our results have robust implications for future more informed deployment of effective vaccination campaigns, beyond the sole consideration of coverage and encourage frequent mass drug administration of praziquantel in schistosomiasis-endemic areas to ensure the sustainability of vaccine elicited responses thus protection of the hosts against vaccine preventable diseases. 2022-08-18T20:10:14Z 2022-08-18T20:10:14Z 2022 2022-08-18T17:29:46Z Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/36701 eng application/pdf Department of Pathology Faculty of Health Sciences |
| spellingShingle | pathology Musaigwa, Fungai Impact of the parasitic helminth Schistosoma mansoni on host anti-viral vaccine responses: proof of concept from the anti-polio vaccine |
| thesis_degree_str | Doctoral |
| title | Impact of the parasitic helminth Schistosoma mansoni on host anti-viral vaccine responses: proof of concept from the anti-polio vaccine |
| title_full | Impact of the parasitic helminth Schistosoma mansoni on host anti-viral vaccine responses: proof of concept from the anti-polio vaccine |
| title_fullStr | Impact of the parasitic helminth Schistosoma mansoni on host anti-viral vaccine responses: proof of concept from the anti-polio vaccine |
| title_full_unstemmed | Impact of the parasitic helminth Schistosoma mansoni on host anti-viral vaccine responses: proof of concept from the anti-polio vaccine |
| title_short | Impact of the parasitic helminth Schistosoma mansoni on host anti-viral vaccine responses: proof of concept from the anti-polio vaccine |
| title_sort | impact of the parasitic helminth schistosoma mansoni on host anti viral vaccine responses proof of concept from the anti polio vaccine |
| topic | pathology |
| url | http://hdl.handle.net/11427/36701 |
| work_keys_str_mv | AT musaigwafungai impactoftheparasitichelminthschistosomamansonionhostantiviralvaccineresponsesproofofconceptfromtheantipoliovaccine |