Oligomannose-coated liposome-entrapped dense granule protein 7 induces protective immune response to Neospora caninum in cattle
Oligomannose-coated liposome-entrapped dense granule protein 7 induces protective immune response to Neospora caninum in cattle
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DOI：
10.1016/j.vaccine.2013.05.083
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发表时间：
2013-08-02
期刊：
影响因子：
5.5
通讯作者：
Nishikawa, Yoshifumi
中科院分区：
文献类型：
--
作者：
Nishimura, Maki;Kohara, Junko;Nishikawa, Yoshifumi
犬新孢子虫是一种细胞内原生动物寄生虫，可导致奶牛流产。疫苗接种是控制新孢子虫病的重要策略，需要一种安全有效的牛用疫苗。N.犬NcGRA 7是一种分泌性高抗原性蛋白。我们以前证明，NcGRA 7包埋在脂质体包被甘露三糖（M3-NcGRA 7）可以诱导寄生虫特异性T辅助细胞1型免疫反应，并产生体液抗体，导致后代存活率增加和减少感染的小鼠母鼠的大脑。在本研究中，M3-NcGRA 7作为抗N.已在牛（n = 12）中评价了犬。用含有50 μ g（n = 4）或200 μ g NcGRA 7（n = 4）的M3-NcGRA 7皮下免疫牛两次，间隔4周，并且在第二次免疫后27天用10（7）个Nc-1菌株的速殖子接种所有牛，包括未免疫的对照（n = 4），并在感染后（dpi）85-87天安乐死。在免疫牛中，在攻击前诱导PBMC中的NcGRA 7特异性抗体产生和IFN-γ产生。在3 dpi，体温和血清IFN-γ浓度往往高于对照牛比免疫牛。此外，与对照相比，用50 μ g M3-NcGRA 7免疫的牛脑中的寄生虫负荷显著降低。这些结果表明，M3-NcGRA 7可以诱导针对N.牛的犬速殖子，这可能会导致实际应用的安全和有效的亚单位疫苗。(c)2013爱思唯尔有限公司保留所有权利。
Neospora caninum is an intracellular protozoan parasite that causes abortion in cows. Vaccination is an important strategy for control of neosporosis, and a safe and effective vaccine suitable for cattle is required. Dense granule protein 7 of N. caninum (NcGRA7) is a secretory protein with high antigenicity in hosts. We demonstrated previously that NcGRA7 entrapped in liposomes coated with mannotriose (M3-NcGRA7) could induce a parasite-specific T-helper type 1 immune response and produce humoral antibodies that resulted in increased offspring survival and decreased infection in the brains of mice dams. In the present study, the efficacy of M3-NcGRA7 as a vaccine candidate against N. caninum has been evaluated in cattle (n = 12). Cattle were immunized with M3-NcGRA7 containing 50 mu g (n = 4) or 200 mu g NcGRA7 (n = 4) subcutaneously twice with a 4-week interval and all cattle including the non-immunized controls (n = 4) were inoculated with 10(7) tachyzoites of Nc-1 strain 27 days after the second immunization and euthanized at 85-87 days post infection (dpi). In immunized cattle, NcGRA7-specific antibody production and IFN-gamma production in PBMC was induced before challenge. At 3 dpi, body temperature and concentration of serum IFN-gamma tended to be higher in control cattle than in the immunized cattle. Furthermore, the parasite load in the brain significantly decreased in cattle immunized with 50 mu g M3-NcGRA7 compared with controls. These results suggest that M3-NcGRA7 can induce protective immune responses to N. caninum tachyzoites in cattle, which could lead to practical application of safe and effective subunit vaccines. (c) 2013 Elsevier Ltd. All rights reserved.