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

Guy El Helou; Todd A. Ponzio; Joseph F. Goodman; Maria Blevins; David L. Caudell; Kanakatte S. Raviprakash; Daniel Ewing; Maya Williams; Kevin R. Porter; John W. Sanders

doi:10.1186/s40794-020-00111-5

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

Guy El Helou^*, Todd A. Ponzio, Joseph F. Goodman, Maria Blevins, David L. Caudell, Kanakatte S. Raviprakash, Daniel Ewing, Maya Williams, Kevin R. Porter, John W. Sanders

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

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.

Original language	English
Article number	10
Journal	Tropical Diseases, Travel Medicine and Vaccines
Volume	6
Issue number	1
DOIs	https://doi.org/10.1186/s40794-020-00111-5
State	Published - 3 Jun 2020
Externally published	Yes

Keywords

DNA vaccine
Non-human primate
Salivary gland infusion
Tetravalent dengue vaccine

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10.1186/s40794-020-00111-5

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El Helou, G., Ponzio, T. A., Goodman, J. F., Blevins, M., Caudell, D. L., Raviprakash, K. S., Ewing, D., Williams, M., Porter, K. R., & Sanders, J. W. (2020). Tetravalent dengue DNA vaccine is not immunogenic when delivered by retrograde infusion into salivary glands. Tropical Diseases, Travel Medicine and Vaccines, 6(1), Article 10. https://doi.org/10.1186/s40794-020-00111-5

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title = "Tetravalent dengue DNA vaccine is not immunogenic when delivered by retrograde infusion into salivary glands",

abstract = "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.",

keywords = "DNA vaccine, Non-human primate, Salivary gland infusion, Tetravalent dengue vaccine",

author = "{El Helou}, Guy and Ponzio, {Todd A.} and Goodman, {Joseph F.} and Maria Blevins and Caudell, {David L.} and Raviprakash, {Kanakatte S.} and Daniel Ewing and Maya Williams and Porter, {Kevin R.} and Sanders, {John W.}",

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T1 - Tetravalent dengue DNA vaccine is not immunogenic when delivered by retrograde infusion into salivary glands

AU - El Helou, Guy

AU - Ponzio, Todd A.

AU - Goodman, Joseph F.

AU - Blevins, Maria

AU - Caudell, David L.

AU - Raviprakash, Kanakatte S.

AU - Ewing, Daniel

AU - Williams, Maya

AU - Porter, Kevin R.

AU - Sanders, John W.

PY - 2020/6/3

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N2 - 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.

AB - 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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KW - Non-human primate

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

Abstract

Keywords

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