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

IF 2.4 Q3 INFECTIOUS DISEASES

Tropical Diseases, Travel Medicine and Vaccines Pub Date : 2020-06-03 eCollection Date: 2020-01-01 DOI:10.1186/s40794-020-00111-5

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

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引用次数: 2

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.

Abstract Image

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四价登革热DNA疫苗逆行输注进入唾液腺后不具有免疫原性。

介绍和背景:登革热病毒的四价DNA疫苗正在研制中，但尚未达到最佳的免疫原性。据报道，唾液腺疫苗对啮齿动物和狗有效。我们报告了一项在非人类灵长类动物模型中测试唾液腺作为登革热DNA疫苗平台的初步研究。材料与方法:以4只食蟹猕猴为研究对象。每只猕猴预先服用阿托品和氯胺酮镇静。Stensen的导管乳头用P10聚乙烯管插管，与500毫升注射器相连。在前两次注射中，所有的猕猴都注射了300ul的TVDV和2mg的锌。第三次输注时，为增加唾液组织转染，2只动物给予100uL TVDV混合400uL聚乙烯亚胺1μg/ml (PEI)，另外2只动物给予500uL TVDV加锌。在第二次和第三次输注后4周评估抗体滴度。结果与结论:经Stensen导管行SGRI是一种耐受性良好、操作简单、易复制的手术。在猕猴唾液腺内注入TVDV后，其抗体反应明显弱于其他输注方式。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tropical Diseases, Travel Medicine and Vaccines Multiple-

CiteScore

5.20

自引率

0.00%

发文量

审稿时长

17 weeks

期刊介绍： Tropical Diseases, Travel Medicine and Vaccines is an open access journal that considers basic, translational and applied research, as well as reviews and commentary, related to the prevention and management of healthcare and diseases in international travelers. Given the changes in demographic trends of travelers globally, as well as the epidemiological transitions which many countries are experiencing, the journal considers non-infectious problems including chronic disease among target populations of interest as well as infectious diseases.