Trent Amanda, Ulery Bret D, Black Matthew J, Barrett John C, Liang Simon, Kostenko Yulia, David Natalie A, Tirrell Matthew V
Biomolecular Science and Engineering Program, University of California, Santa Barbara, California, 93106, USA.
AAPS J. 2015 Mar;17(2):380-8. doi: 10.1208/s12248-014-9707-3. Epub 2014 Dec 20.
Delivery system design and adjuvant development are crucially important areas of research for improving vaccines. Peptide amphiphile micelles are a class of biomaterials that have the unique potential to function as both vaccine delivery vehicles and self-adjuvants. In this study, peptide amphiphiles comprised of a group A streptococcus B cell antigen (J8) and a dialkyl hydrophobic moiety (diC16) were synthesized and organized into self-assembled micelles, driven by hydrophobic interactions among the alkyl tails. J8-diC16 formed cylindrical micelles with highly α-helical peptide presented on their surfaces. Both the micelle length and secondary structure were shown to be enhanced by annealing. When injected into mice, J8-diC16 micelles induced a strong IgG1 antibody response that was comparable to soluble J8 peptide supplemented with two classical adjuvants. It was discovered that micelle adjuvanticity requires the antigen be a part of the micelle since separation of J8 and the micelle was insufficient to induce an immune response. Additionally, the diC16 tail appears to be non-immunogenic since it does not stimulate a pathogen recognition receptor whose agonist (Pam3Cys) possesses a very similar chemical structure. The research presented in this paper demonstrates the promise peptide amphiphile micelles have in improving the field of vaccine engineering.
递送系统设计和佐剂开发是改进疫苗的至关重要的研究领域。肽两亲性胶束是一类生物材料,具有作为疫苗递送载体和自佐剂的独特潜力。在本研究中,合成了由A组链球菌B细胞抗原(J8)和二烷基疏水部分(二C16)组成的肽两亲物,并通过烷基尾部之间的疏水相互作用将其组装成自组装胶束。J8-二C16形成了表面呈现高度α-螺旋肽的圆柱形胶束。通过退火显示胶束长度和二级结构均得到增强。当注射到小鼠体内时,J8-二C16胶束诱导出强烈的IgG1抗体反应,这与补充了两种经典佐剂的可溶性J8肽相当。研究发现,胶束佐剂活性要求抗原成为胶束的一部分,因为J8与胶束分离不足以诱导免疫反应。此外,二C16尾部似乎无免疫原性,因为它不会刺激其激动剂(Pam3Cys)具有非常相似化学结构的病原体识别受体。本文提出的研究证明了肽两亲性胶束在改善疫苗工程领域方面的前景。