Ismael Alaa Bassuny, Sekkai Dalila, Collin Christine, Bout Daniel, Mévélec Marie-Noëlle
UMR Université-INRA d'Immunologie Parasitaire et Vaccinologie, UFR des Sciences Pharmaceutiques, IFR Imagerie et Exploration Fonctionnelles, 37200 Tours, France.
Infect Immun. 2003 Nov;71(11):6222-8. doi: 10.1128/IAI.71.11.6222-6228.2003.
Infection with the intracellular protozoan parasite Toxoplasma gondii causes serious public health problems and is of great economic importance worldwide. The micronemal protein MIC3, which is a potent adhesin of T. gondii, could be a significant candidate vaccine against toxoplasmosis. In this study, all CBA/J mice intramuscularly vaccinated with a plasmid encoding the immature form of the MIC3 protein (pMIC3i) produced specific anti-MIC3 immunoglobulin G (IgG) antibodies, and their sera displayed high antibody titers. This response was increased by the coadministration of a plasmid encoding the granulocyte-macrophage colony-stimulating factor (pGM-CSF). Similarly, a specific and significant cellular immune response was obtained in mice immunized with pMIC3i, and this response was markedly enhanced by pGM-CSF coadministration. The cellular immune response was associated with the production of gamma interferon IFN-gamma and interleukin-2 (IL-2), indicating that this was a Th1-type response. This was confirmed by the production of large amounts of IgG2a. Mice immunized with pMIC3i displayed significant protection against an oral challenge with T. gondii 76K cysts, exhibiting fewer brain cysts than did the control mice. Coadministration of pGM-CSF enhanced this protection. In conclusion, this study describes the design of a potent DNA vaccine encoding the novel T. gondii target antigen, MIC3 protein, that elicits a strong specific immune response as well as providing effective protection against T. gondii infection. In the attempt to achieve complete protection against toxoplasmosis, MIC3 is a good candidate vaccine which could be combined with other relevant and previously described candidates, such as SAG1 and GRA4.
细胞内原生动物寄生虫刚地弓形虫感染会引发严重的公共卫生问题,在全球具有重大经济影响。微小膜体蛋白MIC3是刚地弓形虫的一种强效黏附素,可能是预防弓形虫病的重要候选疫苗。在本研究中,所有经肌肉注射编码未成熟形式MIC3蛋白的质粒(pMIC3i)的CBA/J小鼠均产生了特异性抗MIC3免疫球蛋白G(IgG)抗体,且其血清显示出高抗体滴度。通过共同给予编码粒细胞巨噬细胞集落刺激因子的质粒(pGM-CSF),这种反应增强。同样,在用pMIC3i免疫的小鼠中获得了特异性且显著的细胞免疫反应,并且通过共同给予pGM-CSF,这种反应明显增强。细胞免疫反应与γ干扰素IFN-γ和白细胞介素-2(IL-2)的产生相关,表明这是一种Th1型反应。大量IgG2a的产生证实了这一点。用pMIC3i免疫的小鼠对刚地弓形虫76K囊肿的口服攻击显示出显著的保护作用,其脑囊肿比对照小鼠少。共同给予pGM-CSF增强了这种保护作用。总之,本研究描述了一种有效的DNA疫苗的设计,该疫苗编码新型刚地弓形虫靶抗原MIC3蛋白,可引发强烈的特异性免疫反应,并有效预防刚地弓形虫感染。为实现对弓形虫病的完全保护,MIC3是一种良好的候选疫苗,可与其他相关的先前描述的候选疫苗(如SAG1和GRA4)联合使用。