Liang Qian, Li Ruidan, Liu Sijing, Zhang Yunwen, Tian Sicheng, Ou Qian, Chen Zhaobin, Wang Chuan
Department of Public Health Laboratory Sciences, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
Shen Zhen Biomed Alliance Biotech Group Co., Ltd., Shenzhen, China.
Front Microbiol. 2022 Jul 22;13:962326. doi: 10.3389/fmicb.2022.962326. eCollection 2022.
(LM) induces efficient and specific T-cell immune responses in the host. Listeriolysin O (LLO) is the main virulence protein of LM. LLO helps LM escape from the lysosome. However, the pronounced pathogenicity of LM limits its practical application as a live bacterial vector. (LI) also displays intracellular parasitic abilities, cell to cell transfer, and other LM properties, with an elevated biosafety relative to LM. We have confirmed that LI can be used as a viable bacterial vaccine vector. However, we have also observed that LI vector vaccine candidates survive in the immune organ (spleen) for a shorter time compared with the survival time of LM and elicit weaker immune responses compared with LM. Studies have confirmed that hemolysin correlates with some important biological properties of , including cell invasion, intracellular proliferation, and the ability to induce immune responses. We speculated that the weaker immunogenicity of LI compared to LM may be related to the function of ivanolysin O (ILO). Here, we established a hemolysin gene deletion strain, LIΔ, and a modified strain, LIΔ:, whose was replaced by . The hemolysin-modified strain was attenuated; however, it led to significantly improved invasive and proliferative activities of antigen-presenting cells, including those of RAW 264.7 macrophages, compared with the effects of LI. Mice immunized twice with LIΔ: showed higher cytokine levels and better challenge protection rates than LI-immunized mice. This is the first description in carrier vaccine research of the modification of LI hemolysin to obtain a better vaccine carrier than LI. The recombinant strain LIΔ: showed good biosafety and immunogenicity, and thus appears to be a good vector strain for vaccine development.
(单核细胞增生李斯特菌,LM)在宿主体内可诱导高效且特异的T细胞免疫反应。李斯特菌溶血素O(LLO)是LM的主要毒力蛋白。LLO有助于LM从溶酶体中逃逸。然而,LM显著的致病性限制了其作为活细菌载体的实际应用。(伊氏李斯特菌,LI)也表现出细胞内寄生能力、细胞间转移及其他LM的特性,且相对于LM其生物安全性有所提高。我们已证实LI可作为一种可行的细菌疫苗载体。然而,我们也观察到与LM的存活时间相比,LI载体候选疫苗在免疫器官(脾脏)中的存活时间较短,并且与LM相比引发的免疫反应较弱。研究已证实溶血素与LI的一些重要生物学特性相关,包括细胞侵袭、细胞内增殖以及诱导免疫反应的能力。我们推测LI与LM相比免疫原性较弱可能与伊氏溶血素O(ILO)的功能有关。在此,我们构建了一个溶血素基因缺失菌株LIΔ,以及一个修饰菌株LIΔ:,其ILO被LLO取代。溶血素修饰菌株的毒力减弱;然而,与LI相比,它导致抗原呈递细胞(包括RAW 264.7巨噬细胞)的侵袭和增殖活性显著提高。用LIΔ:免疫两次的小鼠比用LI免疫的小鼠表现出更高的细胞因子水平和更好的攻毒保护率。这是在载体疫苗研究中首次描述对LI溶血素进行修饰以获得比LI更好的疫苗载体。重组菌株LIΔ:表现出良好的生物安全性和免疫原性,因此似乎是一种用于疫苗开发的良好载体菌株。