Office of Vaccines Research and Review, Center for Biologics Evaluation and Review, USFDA, Bethesda, Maryland, United States of America.
PLoS One. 2011;6(12):e28164. doi: 10.1371/journal.pone.0028164. Epub 2011 Dec 19.
Given the considerable geographic overlap in the endemic regions for malaria and tuberculosis, it is probable that co-infections with Mycobacterium tuberculosis and Plasmodium species are prevalent. Thus, it is quite likely that both malaria and TB vaccines may be used in the same populations in endemic areas. While novel vaccines are currently being developed and tested individually against each of these pathogens, the efficacy of these vaccines has not been evaluated in co-infection models. To further assess the effectiveness of these new immunization strategies, we investigated whether co-infection with malaria would impact the anti-tuberculosis protection induced by four different types of TB vaccines in a mouse model of pulmonary tuberculosis.
Here we show that the anti-tuberculosis protective immunity induced by four different tuberculosis vaccines was not impacted by a concurrent infection with Plasmodium yoelii NL, a nonlethal form of murine malaria. After an aerogenic challenge with virulent M. tuberculosis, the lung bacterial burdens of vaccinated animals were not statistically different in malaria infected and malaria naïve mice. Multi-parameter flow cytometric analysis showed that the frequency and the median fluorescence intensities (MFI) for specific multifunctional T (MFT) cells expressing IFN-γ, TNF-α, and/or IL-2 were suppressed by the presence of malaria parasites at 2 weeks following the malaria infection but was not affected after parasite clearance at 7 and 10 weeks post-challenge with P. yoelii NL.
Our data indicate that the effectiveness of novel TB vaccines in protecting against tuberculosis was unaffected by a primary malaria co-infection in a mouse model of pulmonary tuberculosis. While the activities of specific MFT cell subsets were reduced at elevated levels of malaria parasitemia, the T cell suppression was short-lived. Our findings have important relevance in developing strategies for the deployment of new TB vaccines in malaria endemic areas.
鉴于疟疾和结核病的流行地区有相当大的地理重叠,结核分枝杆菌和疟原虫属的混合感染很可能很普遍。因此,在流行地区,疟疾和结核病疫苗很可能会在同一人群中使用。虽然目前正在针对这些病原体中的每一种单独开发和测试新型疫苗,但这些疫苗在混合感染模型中的功效尚未得到评估。为了进一步评估这些新免疫策略的有效性,我们研究了疟疾的混合感染是否会影响四种不同类型的结核病疫苗在小鼠肺结核模型中诱导的抗结核保护作用。
在这里,我们表明,四种不同类型的结核病疫苗诱导的抗结核保护作用不受非致死性鼠疟 Plasmodium yoelii NL 混合感染的影响。在用毒力结核分枝杆菌气溶胶挑战后,在疟疾感染和疟疾未感染的小鼠中,接种疫苗动物的肺部细菌负荷在统计学上没有差异。多参数流式细胞术分析表明,在疟疾感染后 2 周,特异性多功能 T(MFT)细胞的频率和中位荧光强度(MFI)表达 IFN-γ、TNF-α 和/或 IL-2 的频率和中位荧光强度(MFI)因疟原虫的存在而受到抑制,但在寄生虫清除后 7 周和 10 周后用 P. yoelii NL 进行挑战后不受影响。
我们的数据表明,在小鼠肺结核模型中,新型结核病疫苗在保护免受结核病方面的有效性不受原发性疟疾混合感染的影响。虽然在疟疾寄生虫血症水平升高时,特定 MFT 细胞亚群的活性受到抑制,但 T 细胞抑制是短暂的。我们的发现对于制定在疟疾流行地区部署新型结核病疫苗的策略具有重要意义。