Vaccine Development Laboratory, Microbiology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.
Center for Biological and Health Sciences, Federal University of Western Bahia, Bahia 47810-047, Brazil.
Viruses. 2020 May 6;12(5):514. doi: 10.3390/v12050514.
In the present study, we evaluated the immunological responses induced by dengue vaccines under experimental conditions after delivery via a transcutaneous (TC) route. Vaccines against type 2 Dengue virus particles (DENV2 New Guinea C (NGC) strain) combined with enterotoxigenic (ETEC) heat-labile toxin (LT) were administered to BALB/c mice in a three-dose immunization regimen via the TC route. As a control for the parenteral administration route, other mouse groups were immunized with the same vaccine formulation via the intradermic (ID) route. Our results showed that mice vaccinated either via the TC or ID routes developed similar protective immunity, as measured after lethal challenges with the DENV2 NGC strain. Notably, the vaccine delivered through the TC route induced lower serum antibody (IgG) responses with regard to ID-immunized mice, particularly after the third dose. The protective immunity elicited in TC-immunized mice was attributed to different antigen-specific antibody properties, such as epitope specificity and IgG subclass responses, and cellular immune responses, as determined by cytokine secretion profiles. Altogether, the results of the present study demonstrate the immunogenicity and protective properties of a dengue vaccine delivered through the TC route and offer perspectives for future clinical applications.
在本研究中，我们评估了经皮（TC）途径递送后实验条件下登革热疫苗引起的免疫反应。将针对 2 型登革病毒颗粒（DENV2 新几内亚 C（NGC）株）的疫苗与肠毒性（ETEC）不耐热毒素（LT）联合，以三剂量免疫方案通过 TC 途径施用于 BALB/c 小鼠。作为对皮下（ID）途径给药途径的对照，其他小鼠组通过相同的疫苗制剂通过 ID 途径进行免疫。我们的结果表明，通过 TC 或 ID 途径接种疫苗的小鼠均产生了相似的保护性免疫，这是在用 DENV2 NGC 株进行致死性攻击后测量的。值得注意的是，与 ID 免疫的小鼠相比，通过 TC 途径递送的疫苗诱导的血清抗体（IgG）反应较低，尤其是在第三剂之后。TC 免疫小鼠中诱导的保护性免疫归因于不同的抗原特异性抗体特性，例如表位特异性和 IgG 亚类反应，以及细胞免疫反应，如细胞因子分泌谱确定。总之，本研究的结果证明了通过 TC 途径递送的登革热疫苗的免疫原性和保护特性，并为未来的临床应用提供了新的思路。
