Cargando…
Recombinant prion protein vaccination of transgenic elk PrP mice and reindeer overcomes self-tolerance and protects mice against chronic wasting disease
Chronic wasting disease (CWD) is a fatal neurodegenerative disease that affects cervids in North America and now Europe. No effective measures are available to control CWD. We hypothesized that active vaccination with homologous and aggregation-prone recombinant prion protein (PrP) could overcome se...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314114/ https://www.ncbi.nlm.nih.gov/pubmed/30397182 http://dx.doi.org/10.1074/jbc.RA118.004810 |
_version_ | 1783384073502195712 |
---|---|
author | Abdelaziz, Dalia H. Thapa, Simrika Brandon, Jenna Maybee, Justine Vankuppeveld, Lauren McCorkell, Robert Schätzl, Hermann M. |
author_facet | Abdelaziz, Dalia H. Thapa, Simrika Brandon, Jenna Maybee, Justine Vankuppeveld, Lauren McCorkell, Robert Schätzl, Hermann M. |
author_sort | Abdelaziz, Dalia H. |
collection | PubMed |
description | Chronic wasting disease (CWD) is a fatal neurodegenerative disease that affects cervids in North America and now Europe. No effective measures are available to control CWD. We hypothesized that active vaccination with homologous and aggregation-prone recombinant prion protein (PrP) could overcome self-tolerance and induce autoantibody production against the cellular isoform of PrP (PrP(C)), which would be protective against CWD infection from peripheral routes. Five groups of transgenic mice expressing elk PrP (TgElk) were vaccinated with either the adjuvant CpG alone or one of four recombinant PrP immunogens: deer dimer (Ddi); deer monomer (Dmo); mouse dimer (Mdi); and mouse monomer (Mmo). Mice were then challenged intraperitoneally with elk CWD prions. All vaccinated mice developed ELISA-detectable antibody titers against PrP. Importantly, all four vaccinated groups survived longer than the control group, with the Mmo-immunized group exhibiting 60% prolongation of mean survival time compared with the control group (183 versus 114 days post-inoculation). We tested for prion infection in brain and spleen of all clinically sick mice. Notably, the attack rate was 100% as revealed by positive CWD signals in all tested tissues when assessed with Western blotting, real-time quaking-induced conversion, and immunohistochemistry. Our pilot study in reindeer indicated appreciable humoral immune responses to Mdi and Ddi immunogens, and the post-immune sera from the Ddi-vaccinated reindeer mitigated CWD propagation in a cell culture model (CWD-RK13). Taken together, our study provides very promising vaccine candidates against CWD, but further studies in cervids are required to investigate vaccine efficacy in the natural CWD hosts. |
format | Online Article Text |
id | pubmed-6314114 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-63141142019-01-03 Recombinant prion protein vaccination of transgenic elk PrP mice and reindeer overcomes self-tolerance and protects mice against chronic wasting disease Abdelaziz, Dalia H. Thapa, Simrika Brandon, Jenna Maybee, Justine Vankuppeveld, Lauren McCorkell, Robert Schätzl, Hermann M. J Biol Chem Molecular Bases of Disease Chronic wasting disease (CWD) is a fatal neurodegenerative disease that affects cervids in North America and now Europe. No effective measures are available to control CWD. We hypothesized that active vaccination with homologous and aggregation-prone recombinant prion protein (PrP) could overcome self-tolerance and induce autoantibody production against the cellular isoform of PrP (PrP(C)), which would be protective against CWD infection from peripheral routes. Five groups of transgenic mice expressing elk PrP (TgElk) were vaccinated with either the adjuvant CpG alone or one of four recombinant PrP immunogens: deer dimer (Ddi); deer monomer (Dmo); mouse dimer (Mdi); and mouse monomer (Mmo). Mice were then challenged intraperitoneally with elk CWD prions. All vaccinated mice developed ELISA-detectable antibody titers against PrP. Importantly, all four vaccinated groups survived longer than the control group, with the Mmo-immunized group exhibiting 60% prolongation of mean survival time compared with the control group (183 versus 114 days post-inoculation). We tested for prion infection in brain and spleen of all clinically sick mice. Notably, the attack rate was 100% as revealed by positive CWD signals in all tested tissues when assessed with Western blotting, real-time quaking-induced conversion, and immunohistochemistry. Our pilot study in reindeer indicated appreciable humoral immune responses to Mdi and Ddi immunogens, and the post-immune sera from the Ddi-vaccinated reindeer mitigated CWD propagation in a cell culture model (CWD-RK13). Taken together, our study provides very promising vaccine candidates against CWD, but further studies in cervids are required to investigate vaccine efficacy in the natural CWD hosts. American Society for Biochemistry and Molecular Biology 2018-12-21 2018-11-05 /pmc/articles/PMC6314114/ /pubmed/30397182 http://dx.doi.org/10.1074/jbc.RA118.004810 Text en © 2018 Abdelaziz et al. Author's Choice—Final version open access under the terms of the Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0) . |
spellingShingle | Molecular Bases of Disease Abdelaziz, Dalia H. Thapa, Simrika Brandon, Jenna Maybee, Justine Vankuppeveld, Lauren McCorkell, Robert Schätzl, Hermann M. Recombinant prion protein vaccination of transgenic elk PrP mice and reindeer overcomes self-tolerance and protects mice against chronic wasting disease |
title | Recombinant prion protein vaccination of transgenic elk PrP mice and reindeer overcomes self-tolerance and protects mice against chronic wasting disease |
title_full | Recombinant prion protein vaccination of transgenic elk PrP mice and reindeer overcomes self-tolerance and protects mice against chronic wasting disease |
title_fullStr | Recombinant prion protein vaccination of transgenic elk PrP mice and reindeer overcomes self-tolerance and protects mice against chronic wasting disease |
title_full_unstemmed | Recombinant prion protein vaccination of transgenic elk PrP mice and reindeer overcomes self-tolerance and protects mice against chronic wasting disease |
title_short | Recombinant prion protein vaccination of transgenic elk PrP mice and reindeer overcomes self-tolerance and protects mice against chronic wasting disease |
title_sort | recombinant prion protein vaccination of transgenic elk prp mice and reindeer overcomes self-tolerance and protects mice against chronic wasting disease |
topic | Molecular Bases of Disease |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314114/ https://www.ncbi.nlm.nih.gov/pubmed/30397182 http://dx.doi.org/10.1074/jbc.RA118.004810 |
work_keys_str_mv | AT abdelazizdaliah recombinantprionproteinvaccinationoftransgenicelkprpmiceandreindeerovercomesselftoleranceandprotectsmiceagainstchronicwastingdisease AT thapasimrika recombinantprionproteinvaccinationoftransgenicelkprpmiceandreindeerovercomesselftoleranceandprotectsmiceagainstchronicwastingdisease AT brandonjenna recombinantprionproteinvaccinationoftransgenicelkprpmiceandreindeerovercomesselftoleranceandprotectsmiceagainstchronicwastingdisease AT maybeejustine recombinantprionproteinvaccinationoftransgenicelkprpmiceandreindeerovercomesselftoleranceandprotectsmiceagainstchronicwastingdisease AT vankuppeveldlauren recombinantprionproteinvaccinationoftransgenicelkprpmiceandreindeerovercomesselftoleranceandprotectsmiceagainstchronicwastingdisease AT mccorkellrobert recombinantprionproteinvaccinationoftransgenicelkprpmiceandreindeerovercomesselftoleranceandprotectsmiceagainstchronicwastingdisease AT schatzlhermannm recombinantprionproteinvaccinationoftransgenicelkprpmiceandreindeerovercomesselftoleranceandprotectsmiceagainstchronicwastingdisease |