Impact of the parasitic helminth Schistosoma mansoni on host anti-viral vaccine responses: proof of concept from the anti-polio vaccine
| dc.contributor.advisor | Nono, Komguep Justin | |
| dc.contributor.advisor | Brombacher, Frank | |
| dc.contributor.author | Musaigwa, Fungai | |
| dc.date.accessioned | 2022-08-18T20:10:14Z | |
| dc.date.available | 2022-08-18T20:10:14Z | |
| dc.date.issued | 2022 | |
| dc.date.updated | 2022-08-18T17:29:46Z | |
| dc.description.abstract | 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. | |
| dc.identifier.apacitation | Musaigwa, F. (2022). <i>Impact of the parasitic helminth Schistosoma mansoni on host anti-viral vaccine responses: proof of concept from the anti-polio vaccine</i>. (). ,Faculty of Health Sciences ,Department of Pathology. Retrieved from http://hdl.handle.net/11427/36701 | en_ZA |
| dc.identifier.chicagocitation | Musaigwa, Fungai. <i>"Impact of the parasitic helminth Schistosoma mansoni on host anti-viral vaccine responses: proof of concept from the anti-polio vaccine."</i> ., ,Faculty of Health Sciences ,Department of Pathology, 2022. http://hdl.handle.net/11427/36701 | en_ZA |
| dc.identifier.citation | Musaigwa, F. 2022. Impact of the parasitic helminth Schistosoma mansoni on host anti-viral vaccine responses: proof of concept from the anti-polio vaccine. . ,Faculty of Health Sciences ,Department of Pathology. http://hdl.handle.net/11427/36701 | en_ZA |
| dc.identifier.ris | TY - Doctoral Thesis AU - Musaigwa, Fungai AB - 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. DA - 2022_ DB - OpenUCT DP - University of Cape Town KW - pathology LK - https://open.uct.ac.za PY - 2022 T1 - Impact of the parasitic helminth Schistosoma mansoni on host anti-viral vaccine responses: proof of concept from the anti-polio vaccine TI - Impact of the parasitic helminth Schistosoma mansoni on host anti-viral vaccine responses: proof of concept from the anti-polio vaccine UR - http://hdl.handle.net/11427/36701 ER - | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11427/36701 | |
| dc.identifier.vancouvercitation | Musaigwa F. Impact of the parasitic helminth Schistosoma mansoni on host anti-viral vaccine responses: proof of concept from the anti-polio vaccine. []. ,Faculty of Health Sciences ,Department of Pathology, 2022 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/36701 | en_ZA |
| dc.language.rfc3066 | eng | |
| dc.publisher.department | Department of Pathology | |
| dc.publisher.faculty | Faculty of Health Sciences | |
| dc.subject | pathology | |
| dc.title | Impact of the parasitic helminth Schistosoma mansoni on host anti-viral vaccine responses: proof of concept from the anti-polio vaccine | |
| dc.type | Doctoral Thesis | |
| dc.type.qualificationlevel | Doctoral | |
| dc.type.qualificationlevel | PhD |