Cargando…

Plant-made polio type 3 stabilized VLPs—a candidate synthetic polio vaccine

Poliovirus (PV) is the causative agent of poliomyelitis, a crippling human disease known since antiquity. PV occurs in two distinct antigenic forms, D and C, of which only the D form elicits a robust neutralizing response. Developing a synthetically produced stabilized virus-like particle (sVLP)-bas...

Descripción completa

Detalles Bibliográficos
Autores principales: Marsian, Johanna, Fox, Helen, Bahar, Mohammad W., Kotecha, Abhay, Fry, Elizabeth E., Stuart, David I., Macadam, Andrew J., Rowlands, David J., Lomonossoff, George P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557999/
https://www.ncbi.nlm.nih.gov/pubmed/28811473
http://dx.doi.org/10.1038/s41467-017-00090-w
_version_ 1783257317652824064
author Marsian, Johanna
Fox, Helen
Bahar, Mohammad W.
Kotecha, Abhay
Fry, Elizabeth E.
Stuart, David I.
Macadam, Andrew J.
Rowlands, David J.
Lomonossoff, George P.
author_facet Marsian, Johanna
Fox, Helen
Bahar, Mohammad W.
Kotecha, Abhay
Fry, Elizabeth E.
Stuart, David I.
Macadam, Andrew J.
Rowlands, David J.
Lomonossoff, George P.
author_sort Marsian, Johanna
collection PubMed
description Poliovirus (PV) is the causative agent of poliomyelitis, a crippling human disease known since antiquity. PV occurs in two distinct antigenic forms, D and C, of which only the D form elicits a robust neutralizing response. Developing a synthetically produced stabilized virus-like particle (sVLP)-based vaccine with D antigenicity, without the drawbacks of current vaccines, will be a major step towards the final eradication of poliovirus. Such a sVLP would retain the native antigenic conformation and the repetitive structure of the original virus particle, but lack infectious genomic material. In this study, we report the production of synthetically stabilized PV VLPs in plants. Mice carrying the gene for the human PV receptor are protected from wild-type PV when immunized with the plant-made PV sVLPs. Structural analysis of the stabilized mutant at 3.6 Å resolution by cryo-electron microscopy and single-particle reconstruction reveals a structure almost indistinguishable from wild-type PV3.
format Online
Article
Text
id pubmed-5557999
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-55579992017-08-17 Plant-made polio type 3 stabilized VLPs—a candidate synthetic polio vaccine Marsian, Johanna Fox, Helen Bahar, Mohammad W. Kotecha, Abhay Fry, Elizabeth E. Stuart, David I. Macadam, Andrew J. Rowlands, David J. Lomonossoff, George P. Nat Commun Article Poliovirus (PV) is the causative agent of poliomyelitis, a crippling human disease known since antiquity. PV occurs in two distinct antigenic forms, D and C, of which only the D form elicits a robust neutralizing response. Developing a synthetically produced stabilized virus-like particle (sVLP)-based vaccine with D antigenicity, without the drawbacks of current vaccines, will be a major step towards the final eradication of poliovirus. Such a sVLP would retain the native antigenic conformation and the repetitive structure of the original virus particle, but lack infectious genomic material. In this study, we report the production of synthetically stabilized PV VLPs in plants. Mice carrying the gene for the human PV receptor are protected from wild-type PV when immunized with the plant-made PV sVLPs. Structural analysis of the stabilized mutant at 3.6 Å resolution by cryo-electron microscopy and single-particle reconstruction reveals a structure almost indistinguishable from wild-type PV3. Nature Publishing Group UK 2017-08-15 /pmc/articles/PMC5557999/ /pubmed/28811473 http://dx.doi.org/10.1038/s41467-017-00090-w Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Marsian, Johanna
Fox, Helen
Bahar, Mohammad W.
Kotecha, Abhay
Fry, Elizabeth E.
Stuart, David I.
Macadam, Andrew J.
Rowlands, David J.
Lomonossoff, George P.
Plant-made polio type 3 stabilized VLPs—a candidate synthetic polio vaccine
title Plant-made polio type 3 stabilized VLPs—a candidate synthetic polio vaccine
title_full Plant-made polio type 3 stabilized VLPs—a candidate synthetic polio vaccine
title_fullStr Plant-made polio type 3 stabilized VLPs—a candidate synthetic polio vaccine
title_full_unstemmed Plant-made polio type 3 stabilized VLPs—a candidate synthetic polio vaccine
title_short Plant-made polio type 3 stabilized VLPs—a candidate synthetic polio vaccine
title_sort plant-made polio type 3 stabilized vlps—a candidate synthetic polio vaccine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557999/
https://www.ncbi.nlm.nih.gov/pubmed/28811473
http://dx.doi.org/10.1038/s41467-017-00090-w
work_keys_str_mv AT marsianjohanna plantmadepoliotype3stabilizedvlpsacandidatesyntheticpoliovaccine
AT foxhelen plantmadepoliotype3stabilizedvlpsacandidatesyntheticpoliovaccine
AT baharmohammadw plantmadepoliotype3stabilizedvlpsacandidatesyntheticpoliovaccine
AT kotechaabhay plantmadepoliotype3stabilizedvlpsacandidatesyntheticpoliovaccine
AT fryelizabethe plantmadepoliotype3stabilizedvlpsacandidatesyntheticpoliovaccine
AT stuartdavidi plantmadepoliotype3stabilizedvlpsacandidatesyntheticpoliovaccine
AT macadamandrewj plantmadepoliotype3stabilizedvlpsacandidatesyntheticpoliovaccine
AT rowlandsdavidj plantmadepoliotype3stabilizedvlpsacandidatesyntheticpoliovaccine
AT lomonossoffgeorgep plantmadepoliotype3stabilizedvlpsacandidatesyntheticpoliovaccine