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Pre-clinical evaluation of a quadrivalent HCV VLP vaccine in pigs following microneedle delivery

The introduction of directly acting antiviral agents (DAAs) has produced significant improvements in the ability to cure chronic hepatitis C infection. However, with over 2% of the world’s population infected with HCV, complications arising from the development of cirrhosis of the liver, chronic hep...

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Autores principales: Christiansen, D., Earnest-Silveira, L., Grubor-Bauk, B., Wijesundara, D. K., Boo, I., Ramsland, P. A., Vincan, E., Drummer, H. E., Gowans, E. J., Torresi, J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592879/
https://www.ncbi.nlm.nih.gov/pubmed/31239471
http://dx.doi.org/10.1038/s41598-019-45461-z
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author Christiansen, D.
Earnest-Silveira, L.
Grubor-Bauk, B.
Wijesundara, D. K.
Boo, I.
Ramsland, P. A.
Vincan, E.
Drummer, H. E.
Gowans, E. J.
Torresi, J.
author_facet Christiansen, D.
Earnest-Silveira, L.
Grubor-Bauk, B.
Wijesundara, D. K.
Boo, I.
Ramsland, P. A.
Vincan, E.
Drummer, H. E.
Gowans, E. J.
Torresi, J.
author_sort Christiansen, D.
collection PubMed
description The introduction of directly acting antiviral agents (DAAs) has produced significant improvements in the ability to cure chronic hepatitis C infection. However, with over 2% of the world’s population infected with HCV, complications arising from the development of cirrhosis of the liver, chronic hepatitis C infection remains the leading indication for liver transplantation. Several modelling studies have indicated that DAAs alone will not be sufficient to eliminate HCV, but if combined with an effective vaccine this regimen would provide a significant advance towards achieving this critical World Health Organisation goal. We have previously generated a genotype 1a, 1b, 2a, 3a HCV virus like particle (VLP) quadrivalent vaccine. The HCV VLPs contain the core and envelope proteins (E1 and E2) of HCV and the vaccine has been shown to produce broad humoral and T cell immune responses following vaccination of mice. In this report we further advanced this work by investigating vaccine responses in a large animal model. We demonstrate that intradermal microneedle vaccination of pigs with our quadrivalent HCV VLP based vaccine produces long-lived multi-genotype specific and neutralizing antibody (NAb) responses together with strong T cell and granzyme B responses and normal Th1 and Th2 cytokine responses. These responses were achieved without the addition of adjuvant. Our study demonstrates that our vaccine is able to produce broad immune responses in a large animal that, next to primates, is the closest animal model to humans. Our results are important as they show that the vaccine can produce robust immune responses in a large animal model before progressing the vaccine to human trials.
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spelling pubmed-65928792019-07-03 Pre-clinical evaluation of a quadrivalent HCV VLP vaccine in pigs following microneedle delivery Christiansen, D. Earnest-Silveira, L. Grubor-Bauk, B. Wijesundara, D. K. Boo, I. Ramsland, P. A. Vincan, E. Drummer, H. E. Gowans, E. J. Torresi, J. Sci Rep Article The introduction of directly acting antiviral agents (DAAs) has produced significant improvements in the ability to cure chronic hepatitis C infection. However, with over 2% of the world’s population infected with HCV, complications arising from the development of cirrhosis of the liver, chronic hepatitis C infection remains the leading indication for liver transplantation. Several modelling studies have indicated that DAAs alone will not be sufficient to eliminate HCV, but if combined with an effective vaccine this regimen would provide a significant advance towards achieving this critical World Health Organisation goal. We have previously generated a genotype 1a, 1b, 2a, 3a HCV virus like particle (VLP) quadrivalent vaccine. The HCV VLPs contain the core and envelope proteins (E1 and E2) of HCV and the vaccine has been shown to produce broad humoral and T cell immune responses following vaccination of mice. In this report we further advanced this work by investigating vaccine responses in a large animal model. We demonstrate that intradermal microneedle vaccination of pigs with our quadrivalent HCV VLP based vaccine produces long-lived multi-genotype specific and neutralizing antibody (NAb) responses together with strong T cell and granzyme B responses and normal Th1 and Th2 cytokine responses. These responses were achieved without the addition of adjuvant. Our study demonstrates that our vaccine is able to produce broad immune responses in a large animal that, next to primates, is the closest animal model to humans. Our results are important as they show that the vaccine can produce robust immune responses in a large animal model before progressing the vaccine to human trials. Nature Publishing Group UK 2019-06-25 /pmc/articles/PMC6592879/ /pubmed/31239471 http://dx.doi.org/10.1038/s41598-019-45461-z Text en © The Author(s) 2019 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
Christiansen, D.
Earnest-Silveira, L.
Grubor-Bauk, B.
Wijesundara, D. K.
Boo, I.
Ramsland, P. A.
Vincan, E.
Drummer, H. E.
Gowans, E. J.
Torresi, J.
Pre-clinical evaluation of a quadrivalent HCV VLP vaccine in pigs following microneedle delivery
title Pre-clinical evaluation of a quadrivalent HCV VLP vaccine in pigs following microneedle delivery
title_full Pre-clinical evaluation of a quadrivalent HCV VLP vaccine in pigs following microneedle delivery
title_fullStr Pre-clinical evaluation of a quadrivalent HCV VLP vaccine in pigs following microneedle delivery
title_full_unstemmed Pre-clinical evaluation of a quadrivalent HCV VLP vaccine in pigs following microneedle delivery
title_short Pre-clinical evaluation of a quadrivalent HCV VLP vaccine in pigs following microneedle delivery
title_sort pre-clinical evaluation of a quadrivalent hcv vlp vaccine in pigs following microneedle delivery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592879/
https://www.ncbi.nlm.nih.gov/pubmed/31239471
http://dx.doi.org/10.1038/s41598-019-45461-z
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