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Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings

Despite mass drug administration programmes with praziquantel, the prevalence of schistosomiasis remains high. A vaccine is urgently needed to control transmission of this debilitating disease. As some promising schistosomiasis vaccine candidates are moving through pre-clinical and clinical testing,...

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Autores principales: Driciru, Emmanuella, Koopman, Jan Pieter R., Cose, Stephen, Siddiqui, Afzal A., Yazdanbakhsh, Maria, Elliott, Alison M., Roestenberg, Meta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970007/
https://www.ncbi.nlm.nih.gov/pubmed/33746974
http://dx.doi.org/10.3389/fimmu.2021.635985
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author Driciru, Emmanuella
Koopman, Jan Pieter R.
Cose, Stephen
Siddiqui, Afzal A.
Yazdanbakhsh, Maria
Elliott, Alison M.
Roestenberg, Meta
author_facet Driciru, Emmanuella
Koopman, Jan Pieter R.
Cose, Stephen
Siddiqui, Afzal A.
Yazdanbakhsh, Maria
Elliott, Alison M.
Roestenberg, Meta
author_sort Driciru, Emmanuella
collection PubMed
description Despite mass drug administration programmes with praziquantel, the prevalence of schistosomiasis remains high. A vaccine is urgently needed to control transmission of this debilitating disease. As some promising schistosomiasis vaccine candidates are moving through pre-clinical and clinical testing, we review the immunological challenges that these vaccine candidates may encounter in transitioning through the clinical trial phases in endemic settings. Prior exposure of the target population to schistosomes and other infections may impact vaccine response and efficacy and therefore requires considerable attention. Schistosomes are known for their potential to induce T-reg/IL-10 mediated immune suppression in populations which are chronically infected. Moreover, endemicity of schistosomiasis is focal whereby target and trial populations may exhibit several degrees of prior exposure as well as in utero exposure which may increase heterogeneity of vaccine responses. The age dependent distribution of exposure and development of acquired immunity, and general differences in the baseline immunological profile, adds to the complexity of selecting suitable trial populations. Similarly, prior or concurrent infections with other parasitic helminths, viral and bacterial infections, may alter immunological responses. Consequently, treatment of co-infections may benefit the immunogenicity of vaccines and may be considered despite logistical challenges. On the other hand, viral infections leave a life-long immunological imprint on the human host. Screening for serostatus may be needed to facilitate interpretation of vaccine responses. Co-delivery of schistosome vaccines with PZQ is attractive from a perspective of implementation but may complicate the immunogenicity of schistosomiasis vaccines. Several studies have reported PZQ treatment to induce both transient and long-term immuno-modulatory effects as a result of tegument destruction, worm killing and subsequent exposure of worm antigens to the host immune system. These in turn may augment or antagonize vaccine immunogenicity. Understanding the complex immunological interactions between vaccine, co-infections or prior exposure is essential in early stages of clinical development to facilitate phase 3 clinical trial design and implementation policies. Besides well-designed studies in different target populations using schistosome candidate vaccines or other vaccines as models, controlled human infections could also help identify markers of immune protection in populations with different disease and immunological backgrounds.
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spelling pubmed-79700072021-03-19 Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings Driciru, Emmanuella Koopman, Jan Pieter R. Cose, Stephen Siddiqui, Afzal A. Yazdanbakhsh, Maria Elliott, Alison M. Roestenberg, Meta Front Immunol Immunology Despite mass drug administration programmes with praziquantel, the prevalence of schistosomiasis remains high. A vaccine is urgently needed to control transmission of this debilitating disease. As some promising schistosomiasis vaccine candidates are moving through pre-clinical and clinical testing, we review the immunological challenges that these vaccine candidates may encounter in transitioning through the clinical trial phases in endemic settings. Prior exposure of the target population to schistosomes and other infections may impact vaccine response and efficacy and therefore requires considerable attention. Schistosomes are known for their potential to induce T-reg/IL-10 mediated immune suppression in populations which are chronically infected. Moreover, endemicity of schistosomiasis is focal whereby target and trial populations may exhibit several degrees of prior exposure as well as in utero exposure which may increase heterogeneity of vaccine responses. The age dependent distribution of exposure and development of acquired immunity, and general differences in the baseline immunological profile, adds to the complexity of selecting suitable trial populations. Similarly, prior or concurrent infections with other parasitic helminths, viral and bacterial infections, may alter immunological responses. Consequently, treatment of co-infections may benefit the immunogenicity of vaccines and may be considered despite logistical challenges. On the other hand, viral infections leave a life-long immunological imprint on the human host. Screening for serostatus may be needed to facilitate interpretation of vaccine responses. Co-delivery of schistosome vaccines with PZQ is attractive from a perspective of implementation but may complicate the immunogenicity of schistosomiasis vaccines. Several studies have reported PZQ treatment to induce both transient and long-term immuno-modulatory effects as a result of tegument destruction, worm killing and subsequent exposure of worm antigens to the host immune system. These in turn may augment or antagonize vaccine immunogenicity. Understanding the complex immunological interactions between vaccine, co-infections or prior exposure is essential in early stages of clinical development to facilitate phase 3 clinical trial design and implementation policies. Besides well-designed studies in different target populations using schistosome candidate vaccines or other vaccines as models, controlled human infections could also help identify markers of immune protection in populations with different disease and immunological backgrounds. Frontiers Media S.A. 2021-03-04 /pmc/articles/PMC7970007/ /pubmed/33746974 http://dx.doi.org/10.3389/fimmu.2021.635985 Text en Copyright © 2021 Driciru, Koopman, Cose, Siddiqui, Yazdanbakhsh, Elliott and Roestenberg. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Driciru, Emmanuella
Koopman, Jan Pieter R.
Cose, Stephen
Siddiqui, Afzal A.
Yazdanbakhsh, Maria
Elliott, Alison M.
Roestenberg, Meta
Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings
title Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings
title_full Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings
title_fullStr Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings
title_full_unstemmed Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings
title_short Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings
title_sort immunological considerations for schistosoma vaccine development: transitioning to endemic settings
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970007/
https://www.ncbi.nlm.nih.gov/pubmed/33746974
http://dx.doi.org/10.3389/fimmu.2021.635985
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