Topuz Ata Derya, Hussain Muattaz, Jones Michael, Best Jonathan, Wiese Martin, Carter Katharine Christine
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK.
Cell Guidance Systems, Babraham Research Campus, Cambridge CB22 3AT, UK.
Microorganisms. 2023 May 17;11(5):1322. doi: 10.3390/microorganisms11051322.
Leishmaniasis is a protozoan disease responsible for significant morbidity and mortality. There is no recommended vaccine to protect against infection. In this study, transgenic expressing gamma glutamyl cysteine synthetase (γGCS) from three pathogenic species were produced and their ability to protect against infection determined using models of cutaneous and visceral leishmaniasis. The ability of IL-2-producing PODS to act as an adjuvant was also determined in studies. Two doses of the live vaccine caused a significant reduction in ( < 0.001) and ( < 0.05) parasite burdens compared to their respective controls. In contrast, immunisation with wild type , using the same immunisation protocol, had no effect on parasite burdens compared to infection controls. Joint treatment with IL-2-producing PODS enhanced the protective effect of the live vaccine in studies. Protection was associated with a Th1 response in and a mixed Th1/Th2 response in , based on specific IgG1 and IgG2a antibody and cytokine production from in vitro proliferation assays using antigen-stimulated splenocytes. The results of this study provide further proof that γGCS should be considered a candidate vaccine for leishmaniasis.
利什曼病是一种由原生动物引起的疾病,会导致严重的发病和死亡。目前尚无推荐的疫苗来预防感染。在本研究中,构建了表达来自三种致病物种的γ-谷氨酰半胱氨酸合成酶(γGCS)的转基因体,并使用皮肤利什曼病和内脏利什曼病模型确定其预防感染的能力。在研究中还确定了产生白细胞介素-2的PODS作为佐剂的能力。与各自的对照组相比,两剂活疫苗导致寄生虫负荷显著降低(<0.001)和(<0.05)。相比之下,使用相同的免疫方案用野生型进行免疫,与感染对照组相比,对寄生虫负荷没有影响。在研究中,与产生白细胞介素-2的PODS联合治疗增强了活疫苗的保护作用。基于使用抗原刺激的脾细胞进行的体外增殖试验中特异性IgG1和IgG2a抗体及细胞因子的产生,在中保护与Th1反应相关,在中与混合的Th1/Th2反应相关。本研究结果进一步证明γGCS应被视为利什曼病的候选疫苗。