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RNA Based Vaccines

机译:基于RNA的疫苗

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摘要

The recognition that CD8~+ T-cell mediated Thl immune responses were necessary to produce immunity to intracellular and transformed self pathogens led to intense interest in the delivery of nucleic acids, DNA, or RNA encoding candidate antigens, as vaccines. Antigen presenting cells (APC) encounter most protein and vaccine immunogens as extracellular proteins and, thus, present them on major histocompatibility complex (MHC) class II molecules leading to the activation of CD4~+ T cells. Protein antigens encoded by nucleic acids delivered to dendritic cell (DC) are produced inside the cell and, thus, can stimulate MHC class I mediated activation of CD8~+ T-cell immune responses. Unfortunately, DCs are not readily transfected with DNA (Ak-bari et al.,1999) resulting in the requirement for high concentrations of DNA and repeated immunizations to achieved immune responses. RNA, on the other hand, is readily taken up and expressed by DC, making it an alternative vaccine candidate. In this article, we will discuss immune responses developed, interactions between APC and RNA that activate and dictate DC activation, and preliminary studies using RNA in vivo and in vitro to develop protective immunity.
机译:CD8 + T细胞介导的Th1免疫应答对于产生针对细胞内和转化的自身病原体的免疫力是必需的这一认识导致人们对作为疫苗的核酸,DNA或编码候选抗原编码的RNA的传递产生了浓厚的兴趣。抗原呈递细胞(APC)作为细胞外蛋白质遇到大多数蛋白质和疫苗免疫原,因此将它们呈递到主要的组织相容性复合体(MHC)II类分子上,从而导致CD4 + T细胞活化。由传递到树突状细胞(DC)的核酸编码的蛋白质抗原在细胞内部产生,因此可以刺激MHC I类介导的CD8 + T细胞免疫应答的激活。不幸的是,DC不容易用DNA转染(Ak-bari等,1999),导致需要高浓度的DNA和重复免疫以获得免疫应答。另一方面,RNA很容易被DC吸收并表达,使其成为备选疫苗。在本文中,我们将讨论开发的免疫应答,激活和指示DC激活的APC与RNA之间的相互作用,以及在体内和体外使用RNA来发展保护性免疫的初步研究。

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