A novel formulation of Mtb72F DNA vaccine for immunization against tuberculosis
A novel formulation of Mtb72F DNA vaccine for immunization against tuberculosis
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DOI：
10.22038/ijbms.2020.41806.9881
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发表时间：
2020-06-01
影响因子：
2.2
通讯作者：
Naderinasab, Mahboubeh
中科院分区：
文献类型：
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作者：
Dalirfardouei, Razieh;Tafaghodi, Mohsen;Naderinasab, Mahboubeh
目的：结核分枝杆菌（M.结核病），一种细胞内病原体，在全球造成150万人死亡。卡介苗（BCG）通常用于保护人们免受M。结核病感染;然而，这种第一代疫苗存在一些障碍。DNA疫苗是第三代结核病疫苗，可诱导细胞免疫应答，对结核病具有保护作用。材料与方法：以TB10.4和/或CpG为佐剂，采用复乳法将质粒Mtb 72 F包埋于PLGA纳米粒中，制备出具有较高免疫原性的DNA疫苗（pcDNA3.1-Mtb 72 F）。结果：制备的纳米粒直径约为250 nm，核酸和蛋白包封率分别为80%和25%。小于200 nm的NP能够促进细胞而不是体液应答。由Mtb 72 F DNA疫苗和包埋在PLGA NPs中的TB10.4组成的制剂的免疫显示出显著的免疫原性，并主要诱导干扰素-γ结果表明，脾细胞培养上清中IFN-γ的表达量明显增加，IFN-γ/IL-4比值明显升高。PLGA纳米颗粒负载Mtb 72 F DNA疫苗与TB 10.4可以被认为是一个有前途的候选疫苗针对结核病。这些结果代表了开发用于结核病保护的新型疫苗的良好的第一步。
Objective(s): Mycobacterium tuberculosis (M. tuberculosis), an intracellular pathogen, causes 1.5 million deaths globally. Bacilli Calmette-Guerin (BCG) is commonly administered to protect people against M. tuberculosis infection; however, there are some obstacles with this first-generation vaccine. DNA vaccines, the third generation vaccines, can induce cellular immune responses for tuberculosis (TB) protection. In this study, optimized DNA vaccine (pcDNA3.1-Mtb72F) entrapped in poly (lacticco-glycolic acid) (PLGA) nanoparticles (NPs) was used to achieve higher immunogenicity.Materials and Methods: Plasmid Mtb72F was formulated in PLGA NPs using double emulsion method in the presence of TB10.4 and/or CpG as an adjuvant. Female BALB/c mice were immunized either with NP-encapsulated Mtb72F or naked Mtb72F with or without each adjuvant, using the BCG-prime DNA boost regimen.Results: These NPs were approximately 250 nm in diameter and the nucleic acid and protein encapsulation efficiency were 80% and 25%, respectively. The NPs smaller than 200 nm are able to promote cellular rather than humoral responses. The immunization with the formulation consisting of Mtb72F DNA vaccine and TB10.4 entrapped in PLGA NPs showed significant immunogenicity and induced predominantly interferon-gamma (IFN-gamma) production and higher INF-gamma/interleukin-4 (IL-4) ratio in the cultured spleen cells supernatant.Conclusion: PLGA NPs loaded with Mtb72F DNA-based vaccine with TB10.4 could be considered as a promising candidate for vaccination against TB. These results represent an excellent initial step toward development of novel vaccine for TB protection.