Schulte Megan C, Boll Adam C, Barcellona Agustin T, Lopez Elida A, Schrum Adam G, Ulery Bret D
Department of Chemical and Biomedical Engineering, University of Missouri, Columbia, MO 65211, USA.
Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65211, USA.
Vaccines (Basel). 2025 Jan 9;13(1):51. doi: 10.3390/vaccines13010051.
BACKGROUND/OBJECTIVES: Peptide amphiphile micelles (PAMs) are an exciting nanotechnology currently being studied for a variety of biomedical applications, especially for drug delivery. Specifically, PAMs can enhance in vivo trafficking, cell-targeting, and cell interactions/internalization. However, modifying peptides, as is commonly performed to induce micellization, can influence their bioactivity. In our previous work, murine antibody responses to PAMs containing the influenza antigen M2 were slightly incongruous with prior PAM vaccine studies using other antigens. In this current work, the effect of native protein linkages and non-native micellizing moieties on M2 immunogenicity was studied.
PAMs were synthesized using an elongated M2 antigen (i.e., PalmK-M2-(KE)). The PAMs were characterized, then their immunogenicity was evaluated with bone marrow-derived dendritic cells and in mice.
Although the modification scheme yielded immunogenic PAMs, these PAMs induced a substantial amount of off-target antibody production compared to unmodified peptidyl micelles (PMs, M2 peptide).
While the impact PAM-induced off-target antibodies had on vaccine efficacy remains to be elucidated, on-target antibodies from both PAM- and PM-vaccinated mice were excitingly able to recognize the M2 antigen within the context of the full M2 protein. This provides preliminary evidence that the PAM-induced on-target antibodies will at minimum be able to recognize the influenza virus upon exposure.
背景/目的：肽两亲性胶束（PAMs）是一种令人兴奋的纳米技术，目前正在针对多种生物医学应用进行研究，尤其是用于药物递送。具体而言，PAMs可以增强体内运输、细胞靶向以及细胞相互作用/内化。然而，像通常为诱导胶束化所进行的那样修饰肽，可能会影响其生物活性。在我们之前的工作中，小鼠对含有流感抗原M2的PAMs的抗体反应与之前使用其他抗原的PAM疫苗研究略有不同。在当前这项工作中，研究了天然蛋白连接和非天然胶束化部分对M2免疫原性的影响。
使用延长的M2抗原（即PalmK-M2-(KE)）合成PAMs。对PAMs进行表征，然后用骨髓来源的树突状细胞和在小鼠体内评估其免疫原性。
尽管修饰方案产生了具有免疫原性的PAMs，但与未修饰的肽基胶束（PMs，M2肽）相比，这些PAMs诱导产生了大量的非靶向抗体。
虽然PAM诱导的非靶向抗体对疫苗效力的影响仍有待阐明，但来自接种PAM和PM疫苗的小鼠的靶向抗体令人兴奋地能够在完整M2蛋白的背景下识别M2抗原。这提供了初步证据，表明PAM诱导的靶向抗体在接触后至少能够识别流感病毒。
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