Tan Ying, Mu Jingqi, Chen Jia
Department of Radiology, The Affiliated People's Hospital of Ningbo University, Ningbo 315040, China.
Microorganisms. 2024 Nov 7;12(11):2258. doi: 10.3390/microorganisms12112258.
can cause congenital infections and abortions in humans. TgIST and TgNSM play critical roles in intracellular cyst formation and chronic infection. However, no studies have explored their potential to induce protective immunity against infection.
To evaluate the immune efficacy of DNA vaccines encoding TgNSM and TgIST genes against infection, using the acute and chronic ME49 strain (Type II).
DNA vaccines, including eukaryotic plasmids pVAX-IST and pVAX-NSM, were constructed. A cocktail DNA vaccine combining these two genes was formulated. The expression and immunogenicity were determined using the indirect immunofluorescence assay (IFA). Mice were immunized with DNA vaccines encoding either TgIST or TgNSM, as well as with the cocktail DNA vaccine. Humoral and cellular immune responses were analyzed by detecting antibody levels, cytotoxic T cell (CTL) responses, cytokines, and lymphocyte surface markers. Mouse survival and brain cyst counts were assessed 1 to 2 months post-vaccination in experimental toxoplasmosis models. The adjuvant efficacy of plasmid pVAX-IL-36γ in enhancing DNA vaccine-induced protective immunity was also evaluated.
DNA immunization with pVAX-IST and pVAX-NSM elicited strong humoral and cellular immune responses, characterized by increased Toxoplasma-specific IgG2a titers, Th1 responses (including production of IFN-γ, IL-2, IL-12p40, and IL-12p70), and cell-mediated activity with elevated frequencies of CD8+ and CD4+ T cells, and CTL responses. This provided significant protective efficacy against acute and chronic infection. Mice immunized with the two-gene cocktail (pVAX-IST + pVAX-NSM) showed greater protection than those immunized with single-gene vaccines. Co-administration of the molecular adjuvant pVAX-IL-36γ further enhanced the protective immunity induced by the cocktail DNA vaccine.
TgIST and TgNSM induce effective immunity against infection, making them promising vaccine candidates against toxoplasmosis. Additionally, IL-36γ is a promising genetic adjuvant that enhances protective immunity in a vaccine setting against , and it should be evaluated in strategies against other apicomplexan parasites.
可导致人类先天性感染和流产。TgIST和TgNSM在细胞内囊肿形成和慢性感染中起关键作用。然而，尚无研究探讨它们诱导针对感染的保护性免疫的潜力。
使用急性和慢性ME49株（II型）评估编码TgNSM和TgIST基因的DNA疫苗对感染的免疫效果。
构建包括真核质粒pVAX-IST和pVAX-NSM在内的DNA疫苗。配制将这两个基因组合的混合DNA疫苗。使用间接免疫荧光法（IFA）测定其表达和免疫原性。用编码TgIST或TgNSM的DNA疫苗以及混合DNA疫苗免疫小鼠。通过检测抗体水平、细胞毒性T细胞（CTL）反应、细胞因子和淋巴细胞表面标志物来分析体液和细胞免疫反应。在实验性弓形虫病模型中，在接种疫苗后1至2个月评估小鼠存活率和脑囊肿数量。还评估了质粒pVAX-IL-36γ在增强DNA疫苗诱导的保护性免疫方面的佐剂效果。
用pVAX-IST和pVAX-NSM进行DNA免疫引发了强烈的体液和细胞免疫反应，其特征为弓形虫特异性IgG2a滴度增加、Th1反应（包括产生IFN-γ、IL-2、IL-12p40和IL-12p70）以及细胞介导活性，CD8 +和CD4 + T细胞频率升高以及CTL反应增强。这为急性和慢性感染提供了显著的保护效果。用双基因混合物（pVAX-IST + pVAX-NSM）免疫的小鼠比用单基因疫苗免疫的小鼠表现出更强的保护作用。分子佐剂pVAX-IL-36γ的共同给药进一步增强了混合DNA疫苗诱导的保护性免疫。
TgIST和TgNSM可诱导针对感染的有效免疫，使其成为有前景的抗弓形虫病疫苗候选物。此外，IL-36γ是一种有前景的基因佐剂，可在疫苗环境中增强针对的保护性免疫，应在针对其他顶复门寄生虫的策略中进行评估。
