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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.

Authors+Show Affiliations

Department of Medicine, Division of Infectious Diseases and Global Medicine, University of Florida, Gainesville, FL USA.Department of Medicine, Division of Infectious Diseases, Wake Forest School of Medicine, Winston-Salem, NC USA.Department of Otolaryngology, George Washington School of Medicine and Health Sciences, Washington, DC 20037 USA.Department of Medicine, Division of Infectious Diseases, Wake Forest School of Medicine, Winston-Salem, NC USA.Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC USA.Naval Medical Research Center, Silver Spring, MD USA.Naval Medical Research Center, Silver Spring, MD USA.Naval Medical Research Center, Silver Spring, MD USA.Naval Medical Research Center, Silver Spring, MD USA.Department of Medicine, Division of Infectious Diseases, Wake Forest School of Medicine, Winston-Salem, NC USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32518668

Citation

El Helou, Guy, et al. "Tetravalent Dengue DNA Vaccine Is Not Immunogenic when Delivered By Retrograde Infusion Into Salivary Glands." Tropical Diseases, Travel Medicine and Vaccines, vol. 6, 2020, p. 10.
El Helou G, Ponzio TA, Goodman JF, et al. Tetravalent dengue DNA vaccine is not immunogenic when delivered by retrograde infusion into salivary glands. Trop Dis Travel Med Vaccines. 2020;6:10.
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, 10. https://doi.org/10.1186/s40794-020-00111-5
El Helou G, et al. Tetravalent Dengue DNA Vaccine Is Not Immunogenic when Delivered By Retrograde Infusion Into Salivary Glands. Trop Dis Travel Med Vaccines. 2020;6:10. PubMed PMID: 32518668.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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, Y1 - 2020/06/03/ PY - 2020/02/15/received PY - 2020/05/25/accepted PY - 2020/6/11/entrez PY - 2020/6/11/pubmed PY - 2020/6/11/medline KW - DNA vaccine KW - Non-human primate KW - Salivary gland infusion KW - Tetravalent dengue vaccine SP - 10 EP - 10 JF - Tropical diseases, travel medicine and vaccines JO - Trop Dis Travel Med Vaccines VL - 6 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. SN - 2055-0936 UR - https://www.unboundmedicine.com/medline/citation/32518668/Tetravalent_dengue_DNA_vaccine_is_not_immunogenic_when_delivered_by_retrograde_infusion_into_salivary_glands L2 - https://tdtmvjournal.biomedcentral.com/articles/10.1186/s40794-020-00111-5 DB - PRIME DP - Unbound Medicine ER -
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