Cargando…
Prevention and Immunotherapy of Secondary Murine Alveolar Echinococcosis Employing Recombinant EmP29 Antigen
Alveolar echinococcosis (AE) is caused by infection with the larval stage of the tapeworm Echinococcus multilocularis. An increasing understanding of immunological events that account for the metacestode survival in human and murine AE infection prompted us to undertake explorative experiments tackl...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4460070/ https://www.ncbi.nlm.nih.gov/pubmed/26053794 http://dx.doi.org/10.1371/journal.pntd.0003795 |
_version_ | 1782375316972371968 |
---|---|
author | Boubaker, Ghalia Hemphill, Andrew Huber, Cristina Olivia Spiliotis, Markus Babba, Hamouda Gottstein, Bruno |
author_facet | Boubaker, Ghalia Hemphill, Andrew Huber, Cristina Olivia Spiliotis, Markus Babba, Hamouda Gottstein, Bruno |
author_sort | Boubaker, Ghalia |
collection | PubMed |
description | Alveolar echinococcosis (AE) is caused by infection with the larval stage of the tapeworm Echinococcus multilocularis. An increasing understanding of immunological events that account for the metacestode survival in human and murine AE infection prompted us to undertake explorative experiments tackling the potential of novel preventive and/or immunotherapeutic measures. In this study, the immunoprotective and immunotherapeutic ability of recombinant EmP29 antigen (rEmP29) was assessed in mice that were intraperitoneally infected with E. multilocularis metacestodes. For vaccination, three intraperitoneal injections with 20μg rEmP29 emulsified in saponin adjuvants were applied over 6 weeks. 2 weeks after the last boost, mice were infected, and at 90 days post-infection, rEmP29-vaccinated mice exhibited a median parasite weight that was reduced by 75% and 59% when compared to NaCl- or saponin–treated control mice, respectively. For immunotherapeutical application, the rEmP29 (20μg) vaccine was administered to experimentally infected mice, starting at 1 month post-infection, three times with 2 weeks intervals. Mice undergoing rEmP29 immunotherapy exhibited a median parasite load that was reduced by 53% and 49% when compared to NaCl- and saponin–treated control mice, respectively. Upon analysis of spleen cells, both, vaccination and treatment with rEmP29, resulted in low ratios of Th2/Th1 (IL-4/IFN-γ) cytokine mRNA and low levels of mRNA coding for IL-10 and IL-2. These results suggest that reduction of the immunosuppressive environment takes place in vaccinated as well as immunotreated mice, and a shift towards a Th1 type of immune response may be responsible for the observed increased restriction of parasite growth. The present study provides the first evidence that active immunotherapy may present a sustainable route for the control of AE. |
format | Online Article Text |
id | pubmed-4460070 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44600702015-06-16 Prevention and Immunotherapy of Secondary Murine Alveolar Echinococcosis Employing Recombinant EmP29 Antigen Boubaker, Ghalia Hemphill, Andrew Huber, Cristina Olivia Spiliotis, Markus Babba, Hamouda Gottstein, Bruno PLoS Negl Trop Dis Research Article Alveolar echinococcosis (AE) is caused by infection with the larval stage of the tapeworm Echinococcus multilocularis. An increasing understanding of immunological events that account for the metacestode survival in human and murine AE infection prompted us to undertake explorative experiments tackling the potential of novel preventive and/or immunotherapeutic measures. In this study, the immunoprotective and immunotherapeutic ability of recombinant EmP29 antigen (rEmP29) was assessed in mice that were intraperitoneally infected with E. multilocularis metacestodes. For vaccination, three intraperitoneal injections with 20μg rEmP29 emulsified in saponin adjuvants were applied over 6 weeks. 2 weeks after the last boost, mice were infected, and at 90 days post-infection, rEmP29-vaccinated mice exhibited a median parasite weight that was reduced by 75% and 59% when compared to NaCl- or saponin–treated control mice, respectively. For immunotherapeutical application, the rEmP29 (20μg) vaccine was administered to experimentally infected mice, starting at 1 month post-infection, three times with 2 weeks intervals. Mice undergoing rEmP29 immunotherapy exhibited a median parasite load that was reduced by 53% and 49% when compared to NaCl- and saponin–treated control mice, respectively. Upon analysis of spleen cells, both, vaccination and treatment with rEmP29, resulted in low ratios of Th2/Th1 (IL-4/IFN-γ) cytokine mRNA and low levels of mRNA coding for IL-10 and IL-2. These results suggest that reduction of the immunosuppressive environment takes place in vaccinated as well as immunotreated mice, and a shift towards a Th1 type of immune response may be responsible for the observed increased restriction of parasite growth. The present study provides the first evidence that active immunotherapy may present a sustainable route for the control of AE. Public Library of Science 2015-06-08 /pmc/articles/PMC4460070/ /pubmed/26053794 http://dx.doi.org/10.1371/journal.pntd.0003795 Text en © 2015 Boubaker et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Boubaker, Ghalia Hemphill, Andrew Huber, Cristina Olivia Spiliotis, Markus Babba, Hamouda Gottstein, Bruno Prevention and Immunotherapy of Secondary Murine Alveolar Echinococcosis Employing Recombinant EmP29 Antigen |
title | Prevention and Immunotherapy of Secondary Murine Alveolar Echinococcosis Employing Recombinant EmP29 Antigen |
title_full | Prevention and Immunotherapy of Secondary Murine Alveolar Echinococcosis Employing Recombinant EmP29 Antigen |
title_fullStr | Prevention and Immunotherapy of Secondary Murine Alveolar Echinococcosis Employing Recombinant EmP29 Antigen |
title_full_unstemmed | Prevention and Immunotherapy of Secondary Murine Alveolar Echinococcosis Employing Recombinant EmP29 Antigen |
title_short | Prevention and Immunotherapy of Secondary Murine Alveolar Echinococcosis Employing Recombinant EmP29 Antigen |
title_sort | prevention and immunotherapy of secondary murine alveolar echinococcosis employing recombinant emp29 antigen |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4460070/ https://www.ncbi.nlm.nih.gov/pubmed/26053794 http://dx.doi.org/10.1371/journal.pntd.0003795 |
work_keys_str_mv | AT boubakerghalia preventionandimmunotherapyofsecondarymurinealveolarechinococcosisemployingrecombinantemp29antigen AT hemphillandrew preventionandimmunotherapyofsecondarymurinealveolarechinococcosisemployingrecombinantemp29antigen AT hubercristinaolivia preventionandimmunotherapyofsecondarymurinealveolarechinococcosisemployingrecombinantemp29antigen AT spiliotismarkus preventionandimmunotherapyofsecondarymurinealveolarechinococcosisemployingrecombinantemp29antigen AT babbahamouda preventionandimmunotherapyofsecondarymurinealveolarechinococcosisemployingrecombinantemp29antigen AT gottsteinbruno preventionandimmunotherapyofsecondarymurinealveolarechinococcosisemployingrecombinantemp29antigen |