Mancha-Agresti Pamela, de Castro Camila Prosperi, Dos Santos Janete S C, Araujo Maíra A, Pereira Vanessa B, LeBlanc Jean G, Leclercq Sophie Y, Azevedo Vasco
Laboratory of Cellular and Molecular Genetics, Department of General Biology, Instituto de Ciências Biológicas - Universidade Federal de Minas GeraisBelo Horizonte, Brazil.
Laboratório de Inovação Biotecnológica, Fundação Ezequiel DiasBelo Horizonte, Brazil.
Front Microbiol. 2017 Jul 11;8:1263. doi: 10.3389/fmicb.2017.01263. eCollection 2017.
Tuberculosis (TB) remains a major threat throughout the world and in 2015 it caused the death of 1.4 million people. The Bacillus Calmette-Guérin is the only existing vaccine against this ancient disease; however, it does not provide complete protection in adults. New vaccines against TB are eminently a global priority. The use of bacteria as vehicles for delivery of vaccine plasmids is a promising vaccination strategy. In this study, we evaluated the use of, an engineered invasive (expressing Fibronectin-Binding Protein A from ) for the delivery of DNA plasmid to host cells, especially to the mucosal site as a new DNA vaccine against tuberculosis. One of the major antigens documented that offers protective responses against is the Ag85A. FnBPA (pValac: which was obtained and used for intranasal immunization of C57BL/6 mice and the immune response profile was evaluated. In this study we observed that this strain was able to produce significant increases in the amount of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6) in the stimulated spleen cell supernatants, showing a systemic T helper 1 (Th1) cell response. Antibody production (IgG and sIgA anti-Ag85A) was also significantly increased in bronchoalveolar lavage, as well as in the serum of mice. In summary, these findings open new perspectives in the area of mucosal DNA vaccine, against specific pathogens using a Lactic Acid Bacteria such as
结核病在全球范围内仍然是一个重大威胁，2015年有140万人死于该病。卡介苗是针对这种古老疾病的唯一现有疫苗；然而，它并不能为成年人提供完全的保护。新型结核病疫苗显然是全球优先事项。利用细菌作为疫苗质粒递送载体是一种很有前景的疫苗接种策略。在本研究中，我们评估了一种经过基因工程改造的侵袭性（表达来自的纤连蛋白结合蛋白A）用于将DNA质粒递送至宿主细胞，特别是递送至黏膜部位，作为一种新型抗结核病DNA疫苗。已证明能提供针对的保护性反应的主要抗原之一是Ag85A。获取了FnBPA（pValac）并用于对C57BL/6小鼠进行鼻内免疫，并评估了免疫反应情况。在本研究中，我们观察到该菌株能够使刺激的脾细胞上清液中促炎细胞因子（IFN-γ、TNF-α和IL-6）的量显著增加，显示出全身性辅助性T细胞1（Th1）细胞反应。支气管肺泡灌洗以及小鼠血清中的抗体产生（抗Ag85A的IgG和sIgA）也显著增加。总之，这些发现为使用乳酸菌等针对特定病原体的黏膜DNA疫苗领域开辟了新的前景。
