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免疫评价:载脂肽抗原与亲脂佐剂的共组装——自佐剂抗乳腺癌疫苗候选物。

Immunological Evaluation of Co-Assembling a Lipidated Peptide Antigen and Lipophilic Adjuvants: Self-Adjuvanting Anti-Breast-Cancer Vaccine Candidates.

机构信息

Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043, Japan.

Core for Medicine and Science Collaborative Research and Education, Project Research Center for Fundamental Sciences, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043, Japan.

出版信息

Angew Chem Int Ed Engl. 2020 Sep 28;59(40):17705-17711. doi: 10.1002/anie.202007999. Epub 2020 Aug 11.

DOI:10.1002/anie.202007999
PMID:32583549
Abstract

Co-assembling vaccines composed of a lipidated HER2-derived antigenic CH401 peptide and either a lipophilic adjuvant, Pam CSK , α-GalCer, or lipid A 506, were evaluated as breast cancer vaccine candidates. This vaccine design was aimed to inherit both antigen multivalency and antigen-specific immunostimulation properties, observed in reported self-adjuvanting vaccine candidates, by using self-assembly and adjuvant-conjugated antigens. Under vaccination concentrations, respective lipophilic adjuvants underwent co-assembly with lipidated CH401, which boosted the anti-CH401 IgG and IgM production. In particular, α-GalCer was responsible for the most significant immune activation. Therefore, the newly developed vaccine design enabled the optimization of adjuvants against the antigenic CH401 peptide in a simple preparatory manner. Overall, the co-assembling vaccine design opens the door for efficient and practical self-adjuvanting vaccine development.

摘要

将脂质化的 HER2 衍生抗原 CH401 肽与脂溶性佐剂 Pam CSK、α-GalCer 或脂质 A 506 共同组装的疫苗被评估为乳腺癌候选疫苗。这种疫苗设计旨在通过使用自组装和抗原缀合的抗原来继承报告的自佐剂疫苗候选物中观察到的抗原多价性和抗原特异性免疫刺激特性。在接种浓度下,各自的脂溶性佐剂与脂质化的 CH401 共同组装,从而增强了抗 CH401 IgG 和 IgM 的产生。特别是,α-GalCer 负责最显著的免疫激活。因此,新开发的疫苗设计能够以简单的制备方式针对抗原 CH401 肽优化佐剂。总的来说,共同组装疫苗设计为高效实用的自佐剂疫苗开发开辟了道路。

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