PilVax——一种新型粘膜疫苗的多肽传递平台

PilVax - a novel peptide delivery platform for the development of mucosal vaccines

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中文摘要:本研究建立了一种新型肽类传递平台PilVax,该平台能够呈递稳定的、高度扩增的肽类,这种肽类可作为非病原性乳酸乳球菌表面A型链球菌M1菌毛结构的一部分。为进一步展示这种平台的构成,研究将模型肽类Ova(324-339)分别插入骨架蛋白Spy0128的3个不同环区,从而在乳酸球菌表面形成了包含大量肽类的菌毛。利用乳酸球菌PilM1-Ova对小鼠进行鼻内免疫能够诱导产生Ova特异性系统免疫和粘膜免疫反应(IgA和IgG)。同时,研究表明,肽类可以插入到PilVax平台中,且能够整合形成相似的结构,但是抗原的菌毛结构不同。PilVax能够作为一种廉价的传递平台生产许多抗人类重要疫病的肽类疫苗。
外文摘要:Peptide vaccines are an attractive strategy to engineer the induction of highly targeted immune responses and avoid potentially allergenic and/or reactogenic protein regions. However, peptides by themselves are often unstable and poorly immunogenic, necessitating the need for an adjuvant and a specialised delivery system. We have developed a novel peptide delivery platform (PilVax) that allows the presentation of a stabilised and highly amplified peptide as part of the group A streptococcus serotype M1 pilus structure (PilM1) on the surface of the non-pathogenic bacterium Lactococcus lactis. To show proof of concept, we have successfully inserted the model peptide Ova(324-339) into 3 different loop regions of the backbone protein Spy0128, which resulted in the assembly of the pilus containing large numbers of peptide on the surface of L. lactis. Intranasal immunisation of mice with L. lactis PilM1-Ova generated measurable Ova-specific systemic and mucosal responses (IgA and IgG). Furthermore, we show that multiple peptides can be inserted into the PilVax platform and that peptides can also be incorporated into structurally similar, but antigenically different pilus structures. PilVax may be useful as a cost-effective platform for the development of peptide vaccines against a variety of important human pathogens.
外文关键词:GROUP-A STREPTOCOCCUS; RECOMBINANT SUBUNIT VACCINES; GRAM-POSITIVE BACTERIA; LACTIC-ACID BACTERIA; LACTOCOCCUS-LACTIS; IMMUNE-RESPONSES; INTRANASAL IMMUNIZATION; ISOPEPTIDE BONDS; SURFACE PROTEIN; CELL EPITOPE
作者:Wagachchi, D; Tsai, JYC; Chalmers, C; Blanchett, S; Loh, JMS; Proft, T
作者单位:新西兰奥克兰大学
期刊名称:SCIENTIFIC REPORTS
期刊影响因子:4.26
出版年份:2018
出版刊次:2
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  1. 编译服务:动物支原体学
  2. 编译者:程金花
  3. 编译时间:2018-03-22