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当与一种候选疫苗中的()抗原联合使用时,佐剂系统的应用可改善针对()感染的先天性和适应性免疫反应。

The Use of an Adjuvant System Improves Innate and Adaptive Immune Response When Associated with a () Antigen in a Vaccine Candidate against () Infection.

作者信息

Mathias Fernando Augusto Siqueira, Ostolin Thais Lopes Valentim Di Paschoale, Reis Levi Eduardo Soares, Cardoso Jamille Mirelle de Oliveira, De Brito Rory Cristiane Fortes, Aguiar Soares Rodrigo Dian de Oliveira, Roatt Bruno Mendes, Vieira Paula Melo de Abreu, Reis Alexandre Barbosa

机构信息

Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto 35400-000, Minas Gerais, Brazil.

Departamento de Análises Clínicas, Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto 35400-000, Minas Gerais, Brazil.

出版信息

Vaccines (Basel). 2023 Feb 9;11(2):395. doi: 10.3390/vaccines11020395.

Abstract

BACKGROUND

The adjuvants' optimal dose and the administration route can directly influence the epitope recognition patterns and profiles of innate response. We aimed to establish the effect and the optimal dose of adjuvant systems for proposing a vaccine candidate to be employed with () .

METHODS

We evaluated the adjuvants saponin (SAP), monophosphoryl lipid A (MPL) and resiquimod (R-848) isolated and combined as adjuvant systems in a lower dose corresponding to 25%, 33%, and 50% of each adjuvant total dose. Male outbred BALB/c mice were divided into 13 groups, SAP, MPL, and R-848 isolated, and the adjuvant systems SAP plus MPL (SM), SAP plus R-848 (SR), and MPL plus R-848 (MR).

RESULTS

SM50 increased levels of all chemokines analyzed and TNF production, while it presented an increased inflammatory cell infiltrate in the skin with macrophage recruitment. Thus, we proposed a vaccine candidate employing () antigen associated with the SM adjuvant system against experimental () challenge. We observed a significant increase in the frequency of cells expressing the central and effector memory CD4 T cells phenotype in immunized mice with the LBSM50. In the liver, there was a decreased parasite load when mice received LBSM50.

CONCLUSIONS

When combined with () antigen, SM50 increases TNF and IFN-γ, which generates central and effector memory CD4 T cells. Therefore, using an adjuvant system can promote an effective innate immune response with the potential to compose future vaccines.

摘要

背景

佐剂的最佳剂量和给药途径可直接影响表位识别模式和固有免疫反应特征。我们旨在确定佐剂系统的效果和最佳剂量,以便提出一种与()一起使用的候选疫苗。

方法

我们评估了分离出来并组合作为佐剂系统的皂苷(SAP)、单磷酰脂质A(MPL)和瑞喹莫德(R - 848),其剂量较低,分别相当于每种佐剂总剂量的25%、33%和50%。雄性远交BALB/c小鼠被分为13组,分别为单独的SAP、MPL和R - 848组,以及佐剂系统SAP加MPL(SM)、SAP加R - 848(SR)和MPL加R - 848(MR)组。

结果

SM50增加了所有分析的趋化因子水平和肿瘤坏死因子(TNF)的产生,同时皮肤中炎症细胞浸润增加,伴有巨噬细胞募集。因此,我们提出了一种候选疫苗,该疫苗采用与SM佐剂系统相关的()抗原,用于应对实验性()攻击。我们观察到,用LBSM50免疫的小鼠中,表达中枢和效应记忆CD4 T细胞表型的细胞频率显著增加。在肝脏中,当小鼠接受LBSM50时,寄生虫负荷降低。

结论

当与()抗原结合时,SM50增加TNF和干扰素 - γ(IFN - γ),从而产生中枢和效应记忆CD4 T细胞。因此,使用佐剂系统可促进有效的固有免疫反应,具有构成未来疫苗的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09ca/9962147/ea1b607d1136/vaccines-11-00395-g001.jpg

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