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Trop Dis Travel Med Vaccines. 2020 Jun 03;6:10. doi: 10.1186/s40794-020-00111-5. eCollection 2020.

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

Tropical diseases, travel medicine and vaccines

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

Affiliations

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

PMID: 32518668 PMCID: PMC7268334 DOI: 10.1186/s40794-020-00111-5

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.

© The Author(s) 2020.

Keywords: DNA vaccine; Non-human primate; Salivary gland infusion; Tetravalent dengue vaccine

Conflict of interest statement

Competing interestsN/A

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