Modulation of Antigen Display on PapMV Nanoparticles Influences Its Immunogenicity.
Modulation of Antigen Display on PapMV Nanoparticles Influences Its Immunogenicity.
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DOI：
10.3390/vaccines9010033
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发表时间：
2021-01-08
期刊：
影响因子：
7.8
通讯作者：
Leclerc D
中科院分区：
文献类型：
--
作者：
Laliberté-Gagné ME;Bolduc M;Garneau C;Olivera-Ugarte SM;Savard P;Leclerc D
背景：木瓜花叶病毒（PapMV）疫苗平台是一种棒状纳米颗粒，由重组 PapMV 外壳蛋白（CP）围绕非编码单链 RNA（ssRNA）模板自组装而成。 PapMV 纳米颗粒通过刺激 Toll 样受体 (TLR) 7 和 8 来诱导先天免疫。疫苗抗原在纳米颗粒表面的展示，与通过 TLR7/8 的共刺激信号相关，确保了对免疫反应的强烈刺激，这对于候选疫苗的开发是理想的。在这项研究中，我们评估了肽抗原的融合位置（无论是在纳米颗粒的表面还是在纳米颗粒的末端）对该抗原的免疫反应的影响。方法：使用来自甲型流感病毒的两种不同的肽作为模型抗原。源自基质蛋白2的保守M2e肽被选为B细胞表位，源自核衣壳的肽被选为细胞毒性T淋巴细胞(CTL)表位。利用分选酶 A (SrtA) 的转肽酶活性，将这些肽偶联在 PapMV CP 上的两个不同位置，即 N 端 (PapMV-N) 或 C 端 (PapMV-C)。分析并比较了两种不同融合环境中针对肽抗原的体液免疫反应和 CD8+ T 细胞介导的免疫反应。还研究了纳米颗粒表面耦合密度的影响。结论：结果表明，与 C 端偶联相比，PapMV CP N 端 (PapMV-N) 肽抗原的偶联导致对偶联肽抗原的免疫应答增强。两个疫苗平台之间的差异与 PapMV-N 疫苗平台刺激 TLR7/8 的能力增强有关。我们还证明，免疫反应的强度随着纳米颗粒表面耦合密度的增加而增加。
Background: The papaya mosaic virus (PapMV) vaccine platform is a rod-shaped nanoparticle made of the recombinant PapMV coat protein (CP) self-assembled around a noncoding single-stranded RNA (ssRNA) template. The PapMV nanoparticle induces innate immunity through stimulation of the Toll-like receptors (TLR) 7 and 8. The display of the vaccine antigen at the surface of the nanoparticle, associated with the co-stimulation signal via TLR7/8, ensures a strong stimulation of the immune response, which is ideal for the development of candidate vaccines. In this study, we assess the impact of where the peptide antigen is fused, whether at the surface or at the extremities of the nanoparticles, on the immune response directed to that antigen. Methods: Two different peptides from influenza A virus were used as model antigens. The conserved M2e peptide, derived from the matrix protein 2 was chosen as the B-cell epitope, and a peptide derived from the nucleocapsid was chosen as the cytotoxic T lymphocytes (CTL) epitope. These peptides were coupled at two different positions on the PapMV CP, the N- (PapMV-N) or the C-terminus (PapMV-C), using the transpeptidase activity of Sortase A (SrtA). The immune responses, both humoral and CD8+ T-cell-mediated, directed to the peptide antigens in the two different fusion contexts were analyzed and compared. The impact of coupling density at the surface of the nanoparticle was also investigated. Conclusions: The results demonstrate that coupling of the peptide antigens at the N-terminus (PapMV-N) of the PapMV CP led to an enhanced immune response to the coupled peptide antigens as compared to coupling to the C-terminus. The difference between the two vaccine platforms is linked to the enhanced capacity of the PapMV-N vaccine platform to stimulate TLR7/8. We also demonstrated that the strength of the immune response increases with the density of coupling at the surface of the nanoparticles.
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DOI：
10.1016/bs.apcsb.2017.04.008
发表时间：
2017
影响因子：
--
作者：
Jacobitz AW;Kattke MD;Wereszczynski J;Clubb RT
通讯作者：
Clubb RT
影响因子：
--
作者：
Hefferon K
通讯作者：
Hefferon K
DOI：
10.1038/nrd.2017.243
发表时间：
2018-04
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Pardi N;Hogan MJ;Porter FW;Weissman D
通讯作者：
Weissman D
影响因子：
7.8
作者：
Hefferon KL
通讯作者：
Hefferon KL
影响因子：
82.9
作者：
Neirynck, S;Deroo, T;Fiers, W
通讯作者：
Fiers, W