免疫原性
表位
肽
抗原
肽疫苗
免疫系统
纳米载体
化学
生物
病毒学
免疫学
生物化学
药物输送
有机化学
作者
Mazda Rad‐Malekshahi,Marieke F. Fransen,Małgorzata Krawczyk,Mercedeh Mansourian,Meriem Bourajjaj,Jian Chen,Ferry Ossendorp,Wim E. Hennink,Enrico Mastrobattista,Maryam Amidi
标识
DOI:10.1021/acs.molpharmaceut.6b01003
摘要
The aim of the present study was to improve the immunogenicity of peptide epitope vaccines using novel nanocarriers based on self-assembling materials. Several studies demonstrated that peptide antigens in nanoparticulate form induce stronger immune responses than their soluble forms. However, several issues such as poor loading and risk of inducing T cell anergy due to premature release of antigenic epitopes have challenged the clinical success of such systems. In the present study, we developed two vaccine delivery systems by appending a self-assembling peptide (Ac-AAVVLLLW-COOH) or a thermosensitive polymer poly(N-isopropylacrylamide (pNIPAm) to the N-terminus of different peptide antigens (OVA250–264, HPV-E743–57) to generate self-assembling peptide epitopes (SAPEs). The obtained results showed that the SAPEs were able to form nanostructures with a diameter from 20 to 200 nm. The SAPEs adjuvanted with CpG induced and expanded antigen-specific CD8+ T cells in mice. Furthermore, tumor-bearing mice vaccinated with SAPEs harboring the HPV E743–57 peptide showed a delayed tumor growth and an increased survival compared to sham-treated mice. In conclusion, self-assembling peptide based systems increase the immunogenicity of peptide epitope vaccines and therefore warrants further development toward clinical use.
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