Mao Jie, Eom Gi-Deok, Yoon Keon-Woong, Heo Su In, Kang Hae-Ji, Chu Ki Back, Moon Eun-Kyung, Quan Fu-Shi
Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
Department of Microbiology, Dongguk University College of Medicine, Gyeongju 38066, Republic of Korea.
Acta Trop. 2025 Jan;261:107501. doi: 10.1016/j.actatropica.2024.107501. Epub 2024 Dec 16.
Protective efficacy assessment of toxoplasmosis vaccines, at least at the preclinical level, frequently involves lethal dose challenge infection. Nonetheless, their efficacies remain largely unexplored against low infection doses which better reflects how humans become infected in the real world. In this study, we compared the immunity elicited in mice that were heterologously immunized with recombinant baculovirus and virus-like particles expressing either the cyst wall protein (CST1) or microneme protein 8 (MIC8) of Toxoplasma gondii (T. gondii). We also investigated how these vaccines fared against both light and heavy infection intensities of T. gondii ME49. Interestingly, under light infection intensity, vaccines expressing CST1 induced significantly higher mucosal antibody responses than MIC8. Germinal center B (GC B) cell responses were elicited to a greater extent following immunization with either antigen, regardless of the infection dose. Similarly, both antigens suppressed IFN-γ production in the brains upon heavy infection. The overall vaccine-induced protection was also similar for the two vaccine antigens under heavy infection. However, in lightly infected mice, CST1 conferred improved GC B cell induction and further inhibited IFN-γ and cyst burden than those elicited by MIC8, thereby contributing to better protection. These findings indicated that light infection could be used to identify optimal vaccine candidates, thus highlighting the impact of infection intensity in vaccine efficacy evaluations.
弓形虫疫苗的保护效力评估，至少在临床前水平，通常涉及致死剂量的攻毒感染。然而，它们对低感染剂量的效力在很大程度上仍未得到探索，而低感染剂量更能反映人类在现实世界中的感染方式。在本研究中，我们比较了用表达刚地弓形虫囊肿壁蛋白（CST1）或微小膜泡蛋白8（MIC8）的重组杆状病毒和病毒样颗粒进行异源免疫的小鼠所产生的免疫力。我们还研究了这些疫苗在面对刚地弓形虫ME49的轻度和重度感染强度时的表现。有趣的是，在轻度感染强度下，表达CST1的疫苗诱导的黏膜抗体反应显著高于MIC8。无论感染剂量如何，用任何一种抗原免疫后，生发中心B（GC B）细胞反应都有更大程度的激发。同样，在重度感染时，两种抗原都抑制了大脑中IFN-γ的产生。在重度感染下，两种疫苗抗原诱导的总体保护效果也相似。然而，在轻度感染的小鼠中，CST1比MIC8诱导了更好的GC B细胞反应，并进一步抑制了IFN-γ和囊肿负荷，从而提供了更好的保护。这些发现表明，轻度感染可用于识别最佳疫苗候选物，从而突出了感染强度在疫苗效力评估中的影响。
