Wagachchi Dasun, Tsai Jia-Yun C, Chalmers Callum, Blanchett Sam, Loh Jacelyn M S, Proft Thomas
Department of Molecular Medicine & Pathology, School of Medical Sciences, The University of Auckland, Auckland, 1023, New Zealand.
Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, 1023, New Zealand.
Sci Rep. 2018 Feb 7;8(1):2555. doi: 10.1038/s41598-018-20863-7.
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 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.
肽疫苗是一种颇具吸引力的策略,可用于设计诱导高度靶向的免疫反应,并避免潜在的过敏原性和/或反应原性蛋白质区域。然而,肽本身往往不稳定且免疫原性较差,因此需要佐剂和专门的递送系统。我们开发了一种新型的肽递送平台(PilVax),该平台能够在无致病力的乳酸乳球菌表面呈现稳定且高度扩增的肽,作为A组链球菌M1型菌毛结构(PilM1)的一部分。为了证明概念,我们已成功将模型肽Ova插入主链蛋白Spy0128的3个不同环区域,这导致在乳酸乳球菌表面组装含有大量肽的菌毛。用乳酸乳球菌PilM1-Ova对小鼠进行鼻内免疫可产生可测量的Ova特异性全身和黏膜反应(IgA和IgG)。此外,我们表明多种肽可插入PilVax平台,并且肽也可掺入结构相似但抗原性不同的菌毛结构中。PilVax作为一种经济高效的平台,可能有助于开发针对多种重要人类病原体的肽疫苗。