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Potential of Lipid Core Peptide Technology as a Novel Self-Adjuvanting Vaccine Delivery System for Multiple Different Synthetic Peptide Immunogens

机译:脂质核心肽技术作为多种不同合成肽免疫原的新型自佐剂疫苗输送系统的潜力

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摘要

This study demonstrates the effectiveness of a novel self-adjuvanting vaccine delivery system for multiple different synthetic peptide immunogens by use of lipid core peptide (LCP) technology. An LCP formulation incorporating two different protective epitopes of the surface antiphagocytic M protein of group A streptococci (GAS)—the causative agents of rheumatic fever and subsequent rheumatic heart disease—was tested in a murine parenteral immunization and GAS challenge model. Mice were immunized with the LCP-GAS formulation, which contains an M protein amino-terminal type-specific peptide sequence (8830) in combination with a conserved non-host-cross-reactive carboxy-terminal C-region peptide sequence (J8) of the M protein. Our data demonstrated immunogenicity of the LCP-8830-J8 formulation in B10.BR mice when coadministered in complete Freund's adjuvant and in the absence of a conventional adjuvant. In both cases, immunization led to induction of high-titer GAS peptide-specific serum immunoglobulin G antibody responses and induction of highly opsonic antibodies that did not cross-react with human heart tissue proteins. Moreover, mice were completely protected from GAS infection when immunized with LCP-8830-J8 in the presence or absence of a conventional adjuvant. Mice were not protected, however, following immunization with an LCP formulation containing a control peptide from a Schistosoma sp. These data support the potential of LCP technology in the development of novel self-adjuvanting multi-antigen component vaccines and point to the potential application of this system in the development of human vaccines against infectious diseases.
机译:这项研究通过使用脂质核心肽(LCP)技术证明了一种针对多种不同的合成肽免疫原的新型自我佐剂疫苗递送系统的有效性。在鼠肠胃外免疫和GAS攻击模型中测试了一种LCP制剂,该制剂结合了A组链球菌(GAS)的表面抗吞噬M蛋白(GAS)的两个不同保护性表位-风湿热和随后的风湿性心脏病的病因。用LCP-GAS制剂免疫小鼠,该制剂包含M蛋白氨基末端类型特异性肽序列(8830)和保守的非宿主交叉反应性羧基末端C区肽序列(J8) M蛋白。我们的数据证明了在完全弗氏佐剂中和不存在常规佐剂的情况下共同施用B10.BR小鼠时LCP-8830-J8制剂具有免疫原性。在这两种情况下,免疫均导致高滴度GAS肽特异性血清免疫球蛋白G抗体反应的诱导,以及与人心脏组织蛋白不发生交叉反应的高声调抗体的诱导。此外,在存在或不存在常规佐剂的情况下,用LCP-8830-J8免疫小鼠后,可完全免受GAS感染。然而,在用含有来自血吸虫属物种的对照肽的LCP制剂免疫后,小鼠没有受到保护。这些数据支持了LCP技术在开发新型自佐剂多抗原成分疫苗中的潜力,并指出了该系统在开发针对传染病的人类疫苗中的潜在应用。

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