Comparative study of α-helical and β-sheet self-assembled peptide nanofiber vaccine platforms: influence of integrated T-cell epitopes.
Comparative study of α-helical and β-sheet self-assembled peptide nanofiber vaccine platforms: influence of integrated T-cell epitopes.
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DOI：
10.1039/d0bm00521e
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发表时间：
2020-06-21
影响因子：
6.6
通讯作者：
Collier JH
中科院分区：
文献类型：
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作者：
Wu Y ;Kelly SH ;Sanchez-Perez L ;Sampson JH ;Collier JH
形成纳米纤维的几种不同的自组装肽系统已被研究作为疫苗平台，但调整它们引起的免疫反应特征的设计原则尚未得到很好的阐明。在这里，我们比较了两种结构不同的肽纳米纤维所引起的免疫反应，一种是β-片纤维系统（Q11），一种是α-螺旋纳米纤维系统（Coil29），假设整合的T细胞表位在后者内可以促进T滤泡辅助细胞（Tfh）的结合，从而提高抗体滴度和质量。尽管两种肽的内部结构明显不同，但纳米纤维表现出惊人的相似的纳米级形态，并且在没有佐剂的情况下，两种肽都能够对偶联肽表位产生强烈的抗体反应。两者都是轻度炎症，但正如假设的那样，Coil29纳米纤维引发了针对共轭模型表位（OVA323-339）和金黄色葡萄球菌疫苗候选肽表位的更高滴度和活性的抗体反应。随后的研究表明，Coil29纳米纤维具有内部CD4+ T细胞表位：Q11纳米纤维需要共组装额外的CD4+ T细胞表位才能具有免疫原性，而Coil29纳米纤维则没有。与Q11纳米纤维相比，Coil29纳米纤维还提高了生发中心B细胞反应和滤泡辅助性T细胞（Tfh）反应，可能有助于改善抗体反应。这些发现说明了改善自组装肽纳米纤维引起的体液反应的设计策略。具有完整T细胞表位的Coil29纳米纤维通过诱导额外的Tfh细胞产生强烈的体液反应和B细胞记忆。
Several different self-assembling peptide systems that form nanofibers have been investigated as vaccine platforms, but design principles for adjusting the character of the immune responses they raise have yet to be well articulated. Here we compared the immune responses raised by two structurally dissimilar peptide nanofibers, one a β-sheet fibrillar system (Q11), and one an α-helical nanofiber system (Coil29), hypothesizing that integrated T-cell epitopes within the latter would promote T follicular helper (Tfh) cell engagement and lead to improved antibody titers and quality. Despite significantly different internal structures, nanofibers of the two peptides exhibited surprisingly similar nanoscale morphologies, and both were capable of raising strong antibody responses to conjugated peptide epitopes in mice without adjuvant. Both were minimally inflammatory, but as hypothesized Coil29 nanofibers elicited antibody responses with higher titers and avidities against a conjugated model epitope (OVA323–339) and a candidate peptide epitope for vaccination against S. aureus. Subsequent investigation indicated that Coil29 nanofibers possessed internal CD4+ T cell epitopes: whereas Q11 nanofibers required co-assembly of additional CD4+ T cell epitopes to be immunogenic, Coil29 nanofibers did not. Coil29 nanofibers also raised stronger germinal center B cell responses and follicular helper T cell (Tfh) responses relative to Q11 nanofibers, likely facilitating the improvement of the antibody response. These findings illustrate design strategies for improving humoral responses raised by self-assembled peptide nanofibers. Coil29 nanofibers with integral T cell epitopes generated strong humoral responses and B cell memory by eliciting additional Tfh cells.
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DOI：
10.1073/pnas.1105200108
发表时间：
2011-09-20
影响因子：
11.1
作者：
Jewell, Christopher M.;Lopez, Sandra C. Bustamante;Irvine, Darrell J.
通讯作者：
Irvine, Darrell J.
影响因子：
16.6
作者：
Francica, Joseph R.;Sheng, Zizhang;Zhang, Zhenhai;Nishimura, Yoshiaki;Shingai, Masashi;Ramesh, Akshaya;Keele, Brandon F.;Schmidt, Stephen D.;Flynn, Barbara J.;Darko, Sam;Lynch, Rebecca M.;Yamamoto, Takuya;Matus-Nicodemos, Rodrigo;Wolinsky, David;Nason, Martha;Valiante, Nicholas M.;Malyala, Padma;De Gregorio, Ennio;Barnett, Susan W.;Singh, Manmohan;O'Hagan, Derek T.;Koup, Richard A.;Mascola, John R.;Martin, Malcolm A.;Kepler, Thomas B.;Douek, Daniel C.;Shapiro, Lawrence;Seder, Robert A.
通讯作者：
Seder, Robert A.
DOI：
10.4049/jimmunol.0901957
发表时间：
2009-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kaba SA;Brando C;Guo Q;Mittelholzer C;Raman S;Tropel D;Aebi U;Burkhard P;Lanar DE
通讯作者：
Lanar DE
DOI：
10.1016/j.jconrel.2015.09.063
发表时间：
2015-12-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
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作者：
Leleux J;Atalis A;Roy K
通讯作者：
Roy K
DOI：
10.1038/nri3804
发表时间：
2015-03
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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