PLGA (85:15) nanoparticle based delivery of rL7/L12 ribosomal protein in mice protects against Brucella abortus 544 infection: A promising alternate to traditional adjuvants
PLGA (85:15) nanoparticle based delivery of rL7/L12 ribosomal protein in mice protects against Brucella abortus 544 infection: A promising alternate to traditional adjuvants
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DOI：
10.1016/j.molimm.2015.09.011
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发表时间：
2015-12-01
影响因子：
3.6
通讯作者：
Bhatnagar, Rakesh
中科院分区：
文献类型：
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作者：
Singh, Damini;Somani, Vikas Kumar;Bhatnagar, Rakesh
迫切需要开发适合人类使用的佐剂，以增强即将到来的疫苗预防危及生命的感染的功效。在目前的研究中，我们试图探索由PLGA（聚乳酸-羟基乙酸共聚物）制成的纳米颗粒（NPs）的免疫原性潜力，PLGA是一种生物可降解和生物相容性聚合物，经FDA批准用于人类使用后，包埋布鲁氏菌的免疫显性抗原rL7/L12蛋白。该制剂显示出佐剂性质，因为它在首次免疫后立即引发高IgG抗体滴度，其在加强给药后显著增加。记录了Th1细胞因子特别是IFN-γ的良好激发。在IgG抗体亚类中，IgG1仍然是免疫后在小鼠血清中引起的主要亚类;然而IgG1/2a比率显示混合的Th1/Th2应答特征。作为细胞免疫扩增标志物的淋巴细胞增殖试验表明，免疫小鼠的脾细胞相对于对照具有高增殖指数，表明包埋L7/L12的PLGA纳米颗粒是对抗布鲁氏菌感染所必需的炎性细胞应答的有效诱导剂。与对照组相比，接种布鲁氏菌544 14天后脾CFU计数显示接种小鼠脾细菌的log CFU显著降低。因此，很明显，在小鼠中递送包埋的疫苗候选物的PLGA纳米制剂引起对包埋的布鲁氏菌抗原特异性的特异性体液应答以及细胞应答。因此，这种方法有很大的希望，通过突出PLGA纳米球的佐剂特性，这项工作将加速开发对人类和兽医使用安全的改良疫苗。(C)2015爱思唯尔有限公司版权所有。
There is a compelling need for the development of suitable adjuvants for human use to enhance the efficacy of the upcoming vaccines for the prevention of life threatening infections. In the current study, we have tried to explore the immunogenic potential of nanoparticles (NPs) made of PLGA (poly lactic-co-glycolic acid), a biodegradable and biocompatible polymer approved by FDA for human use after entrapping rL7/L12 protein, an immunodominant antigen of Brucella. Adjuvant properties were exhibited by the formulation as it elicited high IgG antibody titers just after first immunization which increased significantly after the booster administration. A good elicitation of the Th1 cytokines especially IFN-gamma was recorded. Amongst the IgG antibody subclasses, IgG1 remained the predominant subclass to be elicited in mice serum after immunization; however IgG1/2a ratio showed a mixed profile of Th1/Th2 response. Lymphocyte proliferation assay as a marker of amplification in cellular immunity demonstrated that the splenocytes of the immunized mice had a high proliferation index with reference to the control, revealing that L7/L12 entrapping PLGA nanoparticles are potent inducer of inflammatory cell response indispensable to combat Brucella infection. Enumeration of splenic CFU after 14 days of infection with Brucella abortus 544 showed a significant reduction in log CFU of splenic bacteria in the vaccinated mice as compared to the control group. Therefore it is evident that PLGA nano formulations delivering the entrapped vaccine candidate in mice elicit specific humoral as well as cellular responses specific to the entrapped Brucella antigen. So there is much promise in this approach and this work by highlighting the adjuvant properties of the PLGA nanospheres will accelerate the development of improved vaccines safe for human as well as veterinary use. (C) 2015 Elsevier Ltd. All rights reserved.