Tetravalent dengue DNA vaccine is not immunogenic when delivered by retrograde infusion into salivary glands

INTRODUCTION AND BACKGROUND: A tetravalent DNA vaccine for Dengue virus is under development but has not yet achieved optimal immunogenicity. Salivary glands vaccination has been reported efficacious in rodents and dogs. We report on a pilot study testing the salivary gland as a platform for a Dengu...

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Autores principales: El Helou, Guy, Ponzio, Todd A., Goodman, Joseph F., Blevins, Maria, Caudell, David L., Raviprakash, Kanakatte S., Ewing, Daniel, Williams, Maya, Porter, Kevin R., Sanders, John W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268334/
https://www.ncbi.nlm.nih.gov/pubmed/32518668
http://dx.doi.org/10.1186/s40794-020-00111-5
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author El Helou, Guy
Ponzio, Todd A.
Goodman, Joseph F.
Blevins, Maria
Caudell, David L.
Raviprakash, Kanakatte S.
Ewing, Daniel
Williams, Maya
Porter, Kevin R.
Sanders, John W.
author_facet El Helou, Guy
Ponzio, Todd A.
Goodman, Joseph F.
Blevins, Maria
Caudell, David L.
Raviprakash, Kanakatte S.
Ewing, Daniel
Williams, Maya
Porter, Kevin R.
Sanders, John W.
author_sort El Helou, Guy
collection PubMed
description INTRODUCTION AND BACKGROUND: A tetravalent DNA vaccine for Dengue virus is under development but has not yet achieved optimal immunogenicity. Salivary glands vaccination has been reported efficacious in rodents and dogs. We report on a pilot study testing the salivary gland as a platform for a Dengue DNA vaccine in a non-human primate model. MATERIALS AND METHODS: Four cynomolgus macaques were used in this study. Each macaque was pre-medicated with atropine and sedated with ketamine. Stensen’s duct papilla was cannulated with a P10 polyethylene tube, linked to a 500ul syringe. On the first two infusions, all macaques were infused with 300ul of TVDV mixed with 2 mg of zinc. For the 3rd infusion, to increase transfection into salivary tissue, two animals received 100uL TVDV mixed with 400uL polyethylenimine 1μg/ml (PEI) and the other two animals received 500uL TVDV with zinc. Antibody titers were assessed 4 weeks following the second and third infusion. RESULTS AND CONCLUSIONS: SGRI through Stensen’s duct is a well-tolerated, simple and easy to reproduce procedure. TVDV infused into macaques salivary glands elicited a significantly weaker antibody response than with different delivery methods.
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spelling pubmed-72683342020-06-08 Tetravalent dengue DNA vaccine is not immunogenic when delivered by retrograde infusion into salivary glands El Helou, Guy Ponzio, Todd A. Goodman, Joseph F. Blevins, Maria Caudell, David L. Raviprakash, Kanakatte S. Ewing, Daniel Williams, Maya Porter, Kevin R. Sanders, John W. Trop Dis Travel Med Vaccines Short Report INTRODUCTION AND BACKGROUND: A tetravalent DNA vaccine for Dengue virus is under development but has not yet achieved optimal immunogenicity. Salivary glands vaccination has been reported efficacious in rodents and dogs. We report on a pilot study testing the salivary gland as a platform for a Dengue DNA vaccine in a non-human primate model. MATERIALS AND METHODS: Four cynomolgus macaques were used in this study. Each macaque was pre-medicated with atropine and sedated with ketamine. Stensen’s duct papilla was cannulated with a P10 polyethylene tube, linked to a 500ul syringe. On the first two infusions, all macaques were infused with 300ul of TVDV mixed with 2 mg of zinc. For the 3rd infusion, to increase transfection into salivary tissue, two animals received 100uL TVDV mixed with 400uL polyethylenimine 1μg/ml (PEI) and the other two animals received 500uL TVDV with zinc. Antibody titers were assessed 4 weeks following the second and third infusion. RESULTS AND CONCLUSIONS: SGRI through Stensen’s duct is a well-tolerated, simple and easy to reproduce procedure. TVDV infused into macaques salivary glands elicited a significantly weaker antibody response than with different delivery methods. BioMed Central 2020-06-03 /pmc/articles/PMC7268334/ /pubmed/32518668 http://dx.doi.org/10.1186/s40794-020-00111-5 Text en © The Author(s) 2020 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Short Report
El Helou, Guy
Ponzio, Todd A.
Goodman, Joseph F.
Blevins, Maria
Caudell, David L.
Raviprakash, Kanakatte S.
Ewing, Daniel
Williams, Maya
Porter, Kevin R.
Sanders, John W.
Tetravalent dengue DNA vaccine is not immunogenic when delivered by retrograde infusion into salivary glands
title Tetravalent dengue DNA vaccine is not immunogenic when delivered by retrograde infusion into salivary glands
title_full Tetravalent dengue DNA vaccine is not immunogenic when delivered by retrograde infusion into salivary glands
title_fullStr Tetravalent dengue DNA vaccine is not immunogenic when delivered by retrograde infusion into salivary glands
title_full_unstemmed Tetravalent dengue DNA vaccine is not immunogenic when delivered by retrograde infusion into salivary glands
title_short Tetravalent dengue DNA vaccine is not immunogenic when delivered by retrograde infusion into salivary glands
title_sort tetravalent dengue dna vaccine is not immunogenic when delivered by retrograde infusion into salivary glands
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268334/
https://www.ncbi.nlm.nih.gov/pubmed/32518668
http://dx.doi.org/10.1186/s40794-020-00111-5
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