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基于 PspA、CbpA、PhtD 和 PiuA 抗原免疫显性表位的肺炎球菌候选预防性疫苗的制备及免疫评价。

Production and Immunological Evaluation of Epitope-based Preventative Pneumococcal Candidate Vaccine Comprising Immunodominant Epitopes from PspA, CbpA, PhtD and PiuA Antigens.

机构信息

Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Curr Pharm Biotechnol. 2021 Oct 6;22(14):1900-1909. doi: 10.2174/1389201022666201231112029.

Abstract

BACKGROUND

Streptococcus pneumoniae is the leading cause of pneumonia, mostly in children less than five years and elderly people. Although the Pneumoniae Polysaccharide Vaccine (PPV) and Pneumonia Conjugate Vaccines (PCV) are the efficient pneumococcal vaccine in adults and children, the serotype replacement of S. pneumoniae strains causes the reduction in the efficacy of PPV and PCV vaccines. Epitope-based vaccines are a promising alternative to the present capsular antigen vaccines.

METHODS

In this study, we evaluated cellular and humoral immune responses induced by our novel designed multi-epitope vaccine in BALB/c mice. CD8+ Cytolytic T Lymphocytes (CTLs) epitopes were selected from PspA and CbpA antigens, and CD4+ Helper T Lymphocytes (HTLs) epitopes were chosen from PhtD and PiuA antigens. PorB, the TLR2 agonist, as an adjuvant, was employed to increase the immunogenicity of the vaccine.

RESULTS AND CONCLUSION

The high levels of specific anti-peptide vaccine IgG and an increase in the level of IgG2 in the vaccinated group demonstrated our vaccine could elicit robust antibody production. The significant increase in IFN-γ, IL-2, TNF-α, IL-4, IL-6, and decrease in IL-10 showed that the designed vaccine could be proposed as the efficient preventative pneumococcal vaccine in the mouse model.

摘要

背景

肺炎球菌是导致肺炎的主要原因,主要发生在五岁以下儿童和老年人中。虽然肺炎球菌多糖疫苗(PPV)和肺炎球菌结合疫苗(PCV)是成人和儿童中有效的肺炎球菌疫苗,但肺炎球菌菌株的血清型替代导致 PPV 和 PCV 疫苗的效力降低。基于表位的疫苗是目前荚膜抗原疫苗的一种有前途的替代方法。

方法

在这项研究中,我们评估了新型多表位疫苗在 BALB/c 小鼠中诱导的细胞和体液免疫反应。CD8+细胞毒性 T 淋巴细胞(CTL)表位从 PspA 和 CbpA 抗原中选择,CD4+辅助 T 淋巴细胞(HTL)表位从 PhtD 和 PiuA 抗原中选择。PorB,TLR2 激动剂,作为佐剂,用于提高疫苗的免疫原性。

结果和结论

接种组特异性抗肽疫苗 IgG 水平较高,IgG2 水平升高,表明我们的疫苗能够引起强烈的抗体产生。IFN-γ、IL-2、TNF-α、IL-4、IL-6 水平显著升高,IL-10 水平降低,表明该设计的疫苗可作为小鼠模型中有效的预防性肺炎球菌疫苗。

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