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

• Published in: Tropical Diseases, Travel Medicine and Vaccines
• Main Authors: 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
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2020
• Subjects: Salivary gland infusion; Tetravalent dengue vaccine; DNA vaccine; Non-human primate; Arctic medicine. Tropical medicine; RC955-962; Arctic
• Online Access: https://doi.org/10.1186/s40794-020-00111-5; https://doaj.org/article/96cdbd7afa414679badfde65a9bb1f89

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.