EL-Malky Mohamed A, Al-Harthi Saeed A, Mohamed Raafat T, EL Bali Mohamed A, Saudy Niveen S
Department of Medical Parasitology, Faculty of Medicine, Umm AL-Qura University, Makkah, Kingdom of Saudi Arabia,
Parasitol Res. 2014 Jun;113(6):2277-84. doi: 10.1007/s00436-014-3882-0. Epub 2014 Apr 13.
Toxoplasma gondii (T. gondii) is one of the most successful intracellular protozoan parasites on earth and highly prevalent in most warm-blooded vertebrates. There are no drugs that target the chronic cyst stage of this infection; therefore, development of an effective vaccine would be an important advance in disease control. Oligodeoxynucleotides (ODN) which contain immunostimulatory CG motifs (CpG ODN) can promote T-helper 1 (Th1) responses, an adjuvant activity that is desirable for vaccination against intracellular pathogen. In this study, we compare the immune responses of Toxoplasma susceptible C57BL/6 mice following intranasal and intramuscular vaccination with Toxoplasma lysate antigen (TLA) with or without CpG ODN as adjuvant. Immunized and control non-immunized mice were challenged with 85 cyst of the moderately virulent Beverley strain of T. gondii. Intranasal vaccination gave significantly a higher protection compared to other groups as indicated by prolonged survival and significantly reduced brain cyst burden (P < 0.01). Intranasal vaccination stimulated cellular immunity towards Th1 response characterized by significant INF-γ production (P < 0.01). Furthermore, fecal IgA antibody levels as an indicator of mucosal immune responses were significantly higher (P < 0.05) in intranasal vaccinated group before the challenge compared to all other groups. Intranasal vaccination was not able to upgrade the Th1 humoral arm. In contrast, intramuscular vaccination enhanced humoral immunity towards a type Th1 pattern characterized by a significant increase of specific IgG and Ig2a. Our results suggest that intranasal administration of CpG/TLA would provide a stable, pronounced, and effective vaccine against toxoplasmosis through stimulation of Th1 cellular immunity and mucosal IgA.
刚地弓形虫是地球上最成功的细胞内原生动物寄生虫之一，在大多数温血脊椎动物中高度流行。目前尚无针对该感染慢性囊肿阶段的药物；因此，开发一种有效的疫苗将是疾病控制方面的一项重要进展。含有免疫刺激CG基序的寡脱氧核苷酸（ODN，即CpG ODN）可促进辅助性T细胞1（Th1）反应，这种佐剂活性对于针对细胞内病原体的疫苗接种是理想的。在本研究中，我们比较了易感染弓形虫的C57BL/6小鼠在鼻内和肌肉内接种弓形虫裂解物抗原（TLA）并添加或不添加CpG ODN作为佐剂后的免疫反应。用85个刚地弓形虫中等毒力贝弗利株的囊肿对免疫小鼠和未免疫的对照小鼠进行攻击。与其他组相比，鼻内接种显著提供了更高的保护，表现为存活时间延长和脑囊肿负担显著降低（P< 0.01）。鼻内接种刺激了针对Th1反应 的细胞免疫，其特征是产生显著的INF-γ（P< 0.01）。此外，在攻击前，作为粘膜免疫反应指标的粪便IgA抗体水平在鼻内接种组中显著高于所有其他组（P< 0.05）。鼻内接种无法提升Th1体液免疫分支。相比之下，肌肉内接种增强了针对以特异性IgG和Ig2a显著增加为特征的Th1型体液免疫。我们的结果表明，鼻内给予CpG/TLA通过刺激Th1细胞免疫和粘膜IgA，将提供一种稳定、显著且有效的抗弓形虫病疫苗。
