Engineering Protein Nanoparticles Functionalized with an Immunodominant Coxiella burnetii Antigen to Generate a Q Fever Vaccine.
Engineering Protein Nanoparticles Functionalized with an Immunodominant Coxiella burnetii Antigen to Generate a Q Fever Vaccine.
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DOI：
10.1021/acs.bioconjchem.3c00317
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发表时间：
2023-09-20
影响因子：
4.7
通讯作者：
Wang, Szu-Wen
中科院分区：
文献类型：
--
作者：
Ramirez, Aaron;Felgner, Jiin;Jain, Aarti;Jan, Sharon;Albin, Tyler J.;Badten, Alexander J.;Gregory, Anthony E.;Nakajima, Rie;Jasinskas, Algimantas;Felgner, Philip L.;Burkhardt, Amanda M.;Davies, D. Huw;Wang, Szu-Wen
贝氏柯克斯体是Q热的病原体，目前还没有FDA批准的疫苗。这种细菌病原体在其生命周期中具有细胞外和细胞内阶段，因此细胞介导的（即，T淋巴细胞）和体液（即，抗体）免疫应答是有效根除该病原体所必需的。然而，大多数提议的疫苗仅对一种适应性免疫机制引起强烈应答，并且一些疫苗可引起反应原性或缺乏足够的免疫原性。在这项工作中，我们的目标是应用基于纳米颗粒的平台来产生针对C的抗体和T细胞免疫应答。伯内特氏菌我们研究了将免疫显性外膜蛋白抗原（CBU 1910）缀合至E2纳米颗粒以获得一致的抗原取向的三种方法：直接遗传融合、高亲和力tris-NTA-Ni缀合至多组氨酸标记的CBU 1910和SpyTag/SpyCatcher（ST/SC）系统。总的来说，我们发现ST/SC方法产生了负载有最高数量抗原的纳米颗粒，同时保持稳定性，使得制剂能够在一个纳米颗粒（CBU 1910-CpG-E2）上同时共递送蛋白质抗原（CBU 1910）和佐剂（CpG 1826）。使用蛋白质微阵列分析，我们发现，免疫后，抗原结合的纳米颗粒制剂引起的抗原特异性IgG应答显著高于单独的可溶性CBU 1910，并产生更平衡的IgG 1/IgG 2c比率。尽管与单独的可溶性CBU 1910相比，来自这些蛋白质抗原制剂的T细胞回忆测定未显示抗原特异性IFN-γ产生的显著增加，但与来自CBU 1910的CD 4肽表位缀合的纳米颗粒在小鼠中对CBU 1910肽表位和整个CBU 1910蛋白产生升高的T细胞应答。这些研究强调了将抗原结合到纳米颗粒上以调节和改善体液和细胞介导的针对C.伯内特氏菌
Coxiella burnetii is the causative agent of Q fever, for which there is yet to be an FDA-approved vaccine. This bacterial pathogen has both extra- and intracellular stages in its life cycle, and therefore both a cell-mediated (i.e., T lymphocyte) and humoral (i.e., antibody) immune response are necessary for effective eradication of this pathogen. However, most proposed vaccines elicit strong responses to only one mechanism of adaptive immunity, and some can either cause reactogenicity or lack sufficient immunogenicity. In this work, we aim to apply a nanoparticle-based platform toward producing both antibody and T cell immune responses against C. burnetii. We investigated three approaches for conjugation of the immunodominant outer membrane protein antigen (CBU1910) to the E2 nanoparticle to obtain a consistent antigen orientation: direct genetic fusion, high affinity tris-NTA-Ni conjugation to polyhistidine-tagged CBU1910, and the SpyTag/SpyCatcher (ST/SC) system. Overall, we found that the ST/SC approach yielded nanoparticles loaded with the highest number of antigens while maintaining stability, enabling formulations that could simultaneously co-deliver the protein antigen (CBU1910) and adjuvant (CpG1826) on one nanoparticle (CBU1910-CpG-E2). Using protein microarray analyses, we found that after immunization, antigen-bound nanoparticle formulations elicited significantly higher antigen-specific IgG responses than soluble CBU1910 alone and produced more balanced IgG1/IgG2c ratios. Although T cell recall assays from these protein antigen formulations did not show significant increases in antigen-specific IFN-γ production compared to soluble CBU1910 alone, nanoparticles conjugated with a CD4 peptide epitope from CBU1910 generated elevated T cell responses in mice to both the CBU1910 peptide epitope and whole CBU1910 protein. These investigations highlight the feasibility of conjugating antigens to nanoparticles for tuning and improving both humoral- and cell-mediated adaptive immunity against C. burnetii.
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DOI：
10.4049/jimmunol.1002122
发表时间：
2011-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Duggan JM;You D;Cleaver JO;Larson DT;Garza RJ;Guzmán Pruneda FA;Tuvim MJ;Zhang J;Dickey BF;Evans SE
通讯作者：
Evans SE
影响因子：
9.2
作者：
Nguyen B;Tolia NH
通讯作者：
Tolia NH
影响因子：
3.7
作者：
Chen C;Dow C;Wang P;Sidney J;Read A;Harmsen A;Samuel JE;Peters B
通讯作者：
Peters B
影响因子：
17.1
作者：
Bruun TUJ;Andersson AC;Draper SJ;Howarth M
通讯作者：
Howarth M
影响因子：
8.2
作者：
Li, Enya;Brennan, Caroline K.;Ramirez, Aaron;Tucker, Jo A.;Butkovich, Nina;Meli, Vijaykumar S.;Ionkina, Anastasia A.;Nelson, Edward L.;Prescher, Jennifer A.;Wang, Szu-Wen
通讯作者：
Wang, Szu-Wen