Department of Cell and Molecular Biology, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Ahmedabad, Gujarat, India.
B. R. D. School of Biosciences, Sardar Patel University, Vallabh Vidhyanagar, Gujarat, India.
Gene Ther. 2018 Oct;25(7):485-496. doi: 10.1038/s41434-018-0033-8. Epub 2018 Aug 14.
The non-invasive food grade Lactococcus lactis (L. lactis) represents a safe and attractive alternative to invasive pathogens for the delivery of plasmid DNA at mucosal sites. We have earlier shown the DNA delivery potential of r-L. lactis harboring DNA vaccine reporter plasmid; pPERDBY in vitro. In the present work, we examined in vivo delivery potential of food grade non-invasive r-L. lactis::pPERDBY (LacVax DNA-I) in BALB/c mice. Moreover, using EGFP as a model antigen, we also characterized and compared the immune response elicited by LacVax DNA-I with other conventional vaccination approaches using protein and naked DNA immunization. The presence of antigen-specific serum IgG and fecal secretory IgA (sIgA) antibodies demonstrated in vivo DNA delivery and immune elicitation potential of the developed LacVax DNA-I. As compared with intramuscular injection, oral delivery of pPERDBY via L. lactis resulted in a significantly rapid increase in IgG and higher sIgA titers, indicating the immunogenic and immunostimulatory properties of the LacVax DNA-I. The needle-free immunization with LacVax DNA-I led to increased production of IL-4, an indicator of Th2 screwed response. To the best of our knowledge, this report for the first time outlines comparison of orally administered LacVax DNA-I with other conventional vaccination approaches.
非侵入性食品级乳酸乳球菌（Lactococcus lactis）（L. lactis）代表了一种安全且有吸引力的替代物，可以替代侵袭性病原体，将质粒 DNA 递送到黏膜部位。我们之前已经证明了携带 DNA 疫苗报告质粒的 r-L. lactis （pPERDBY）的 DNA 递送潜力在体外。在本工作中，我们在 BALB/c 小鼠中研究了食品级非侵入性 r-L. lactis::pPERDBY（LacVax DNA-I）的体内递送潜力。此外，使用 EGFP 作为模型抗原，我们还对 LacVax DNA-I 引发的免疫反应进行了表征和比较，其与使用蛋白质和裸露 DNA 免疫的其他常规接种方法进行了比较。存在针对抗原的特异性血清 IgG 和粪便分泌型 IgA（sIgA）抗体，证明了开发的 LacVax DNA-I 的体内 DNA 递送和免疫诱导潜力。与肌肉内注射相比，通过乳球菌递送至 pPERDBY 的口服给药导致 IgG 的快速增加和更高的 sIgA 滴度，表明 LacVax DNA-I 的免疫原性和免疫刺激性。LacVax DNA-I 的无针免疫导致产生更多的 IL-4，这是 Th2 反应的指标。据我们所知，本报告首次概述了口服给予 LacVax DNA-I 与其他常规接种方法的比较。
