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首页> 外文期刊>Infection and immunity >Immunization with a DNA Vaccine Cocktail Protects Mice Lacking CD4 Cells against an Aerogenic Infection with Mycobacterium tuberculosis
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Immunization with a DNA Vaccine Cocktail Protects Mice Lacking CD4 Cells against an Aerogenic Infection with Mycobacterium tuberculosis

机译：用DNA疫苗鸡尾酒免疫可保护缺乏CD4细胞的小鼠免受结核分枝杆菌的气源性感染。

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Tuberculosis (TB) is the most common opportunistic disease and a potentially fatal complication among immunocompromised individuals infected with human immunodeficiency virus (HIV). Effective vaccination against TB in persons with HIV has been considered unlikely because of the central role that CD4 cells play in controlling tuberculous infections. Here we show that the vaccination of CD8?/? mice with a TB DNA vaccine cocktail did not significantly enhance protective responses to a Mycobacterium tuberculosis infection. In contrast, immunization with a DNA vaccine cocktail or with the current TB vaccine, Mycobacterium bovis BCG, induced considerable antituberculosis protective immunity in immune-deficient mice lacking CD4 cells. In vaccinated CD4?/? animals, substantially reduced bacterial burdens in organs and much improved lung pathology were seen 1 month after an aerogenic M. tuberculosis challenge. Importantly, the postchallenge mean times to death of vaccinated CD4?/? mice were significantly extended (mean with DNA cocktail, 172 ± 7 days; mean with BCG, 156 ± 22 days) compared to that of na?ve CD4?/? mice (33 ± 6 days). Furthermore, the treatment of DNA-vaccinated CD4?/? mice with an anti-CD8 or anti-gamma interferon (IFN-γ) antibody significantly reduced the effect of immunization, and neither IFN-γ?/? nor tumor necrosis factor receptor-deficient mice were protected by DNA immunization; therefore, the primary vaccine-induced protective mechanism in these immune-deficient mice likely involves the secretion of cytokines from activated CD8 cells. The substantial CD8-mediated protective immunity that was generated in the absence of CD4 cells suggests that it may be possible to develop effective TB vaccines for use in HIV-infected populations.
机译：结核病（TB）是最常见的机会性疾病，在感染了人类免疫缺陷病毒（HIV）的免疫功能低下的个体中，可能是致命的并发症。由于CD4细胞在控制结核感染中起着核心作用，因此人们认为不太可能对HIV感染者进行有效的TB预防接种。在这里，我们显示了用TB DNA疫苗混合物对CD8 ？/？小鼠进行疫苗接种不会显着增强对结核分枝杆菌感染的保护性反应。相比之下，用DNA疫苗混合物或目前的TB疫苗<牛分枝杆菌 BCG免疫可在缺乏CD4细胞的免疫缺陷小鼠中诱导出显着的抗结核保护性免疫。在接种了CD4 ？/？的动物中，产气的 M 1个月后，器官中的细菌负担大大减少，肺部病理状况大大改善。结核病的挑战。重要的是，与未接种CD4 ？/？的小鼠相比，攻击后平均死亡时间显着延长（DNA鸡尾酒平均为172±7天; BCG平均为156±22天）。五个CD4 ？/？小鼠（33±6天）。此外，用抗CD8或抗γ干扰素（IFN-γ）抗体治疗DNA疫苗接种的CD4 ？/？小鼠可显着降低免疫效果，而IFN-γ？/？或肿瘤坏死因子受体缺陷型小鼠均不受DNA免疫的保护;因此，在这些免疫缺陷小鼠中，疫苗诱导的主要保护机制可能涉及活化CD8细胞分泌细胞因子。在没有CD4细胞的情况下产生的大量CD8介导的保护性免疫表明，可能有可能开发出有效的TB疫苗，用于HIV感染人群。

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