Pan Na, Liu Bohui, Bao Xuemei, Zhang Haochi, Sheng Shouxin, Liang Yanchen, Pan Haiting, Wang Xiao
State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China.
Basic Medical College, Inner Mongolia Medical University, Hohhot 010110, China.
Vaccines (Basel). 2021 Sep 3;9(9):984. doi: 10.3390/vaccines9090984.
is a leading cause of nosocomial and community-associated infection worldwide; however, there is no licensed vaccine available. initiates infection via the mucosa; therefore, a mucosal vaccine is likely to be a promising approach against infection. Lactobacilli, a non-pathogenic bacterium, has gained increasing interest as a mucosal delivery vehicle. Hence, we attempted to develop an oral vaccine based on lactobacilli to cushion the stress of drug resistance and vaccine needs. In this study, we designed, constructed, and evaluated recombinant strains synthesizing nontoxic mutated α-hemolysins (Hla). The results from animal clinical trials showed that recombinant can persist for at least 72 h and can stably express heterologous protein in vivo. Recombinant WXD234 (pNZ8148-Hla) could induce robust mucosal immunity in the GALT, as evidenced by a significant increase in IgA and IL-17 production and the strong proliferation of T-lymphocytes derived from Peyer's patches. WXD234 (pNZ8148-Hla) conferred up to 83% protection against pulmonary infection and significantly reduced the abscess size in a skin infection model. Of particular interest is the sharp reduction of the protective effect offered by WXD234 (pNZ8148-Hla) vaccination in γδ T cell-deficient or IL-17-deficient mice. In conclusion, for the first time, genetically engineered WXD234 (pNZ8148-Hla) as an oral vaccine induced superior mucosal immunity, which was associated with high protection against pulmonary and skin infections caused by . Taken together, our findings suggest the great potential for a delivery system based on lactobacilli and provide experimental data for the development of mucosal vaccines for .
是全球医院感染和社区获得性感染的主要原因；然而，目前尚无获批的疫苗。通过黏膜引发感染；因此，黏膜疫苗可能是预防感染的一种有前景的方法。乳酸杆菌是一种非致病性细菌，作为一种黏膜递送载体越来越受到关注。因此，我们试图开发一种基于乳酸杆菌的口服疫苗，以缓解耐药性和疫苗需求的压力。在本研究中，我们设计、构建并评估了合成无毒突变α-溶血素（Hla）的重组菌株。动物临床试验结果表明，重组菌株可以持续至少72小时，并能在体内稳定表达异源蛋白。重组WXD234（pNZ8148-Hla）可在肠道相关淋巴组织中诱导强大的黏膜免疫，这表现为IgA和IL-17产生显著增加以及派尔集合淋巴结来源的T淋巴细胞强烈增殖。WXD234（pNZ8148-Hla）对肺部感染的保护率高达83%，并在皮肤感染模型中显著减小脓肿大小。特别值得关注的是，在γδT细胞缺陷或IL-17缺陷小鼠中，WXD234（pNZ8148-Hla）疫苗接种提供的保护作用大幅降低。总之，首次将基因工程改造的WXD234（pNZ8148-Hla）作为口服疫苗诱导了卓越的黏膜免疫，这与对由引起的肺部和皮肤感染的高度保护相关。综上所述，我们的研究结果表明基于乳酸杆菌的递送系统具有巨大潜力，并为开发针对的黏膜疫苗提供了实验数据。
