Optimization of Multivalent Gold Nanoparticle Vaccines Eliciting Humoral and Cellular Immunity in an In Vivo Model of Enterohemorrhagic Escherichia coli O157:H7 Colonization.
Optimization of Multivalent Gold Nanoparticle Vaccines Eliciting Humoral and Cellular Immunity in an In Vivo Model of Enterohemorrhagic Escherichia coli O157:H7 Colonization.
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在肠出血性大肠杆菌O157：H7定殖的体内模型中激发体液和细胞免疫的多价金纳米颗粒疫苗的优化。
DOI：
10.1128/msphere.00934-21
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发表时间：
2022-02-23
期刊：
影响因子：
4.8
通讯作者：
Torres AG
中科院分区：
文献类型：
--
作者：
Sanchez-Villamil JI;Tapia D;Torres AG
肠出血性大肠杆菌（EHEC）O157：H7是一种重要的病原体，在世界范围内具有高度的危害性。这一结果的部分原因是与大规模污染产品召回、病原体在带菌者宿主中的流行、疾病后遗症以及与全球几次疫情相关的死亡率相关的高经济影响。此外，抗生素用于治疗EHEC相关感染的禁忌症使得该病原体成为开发有效预防性疫苗的主要候选者。然而，没有任何疫苗被批准用于人类使用，许多疫苗未能提供高度的功效或广泛的保护，从而为使用新技术生产安全，有效和保护性疫苗开辟了道路。基于我们以前使用反向疫苗学预测抗原的研究，我们改进了配方，评估了新的免疫原性抗原，并进一步扩大了我们对EHEC疫苗介导的保护机制的理解。在目前的研究中，我们利用了基于金纳米颗粒（AuNP）的纳米技术平台，它可以作为各种抗原的支架。我们的研究结果表明，一个完善的疫苗制剂纳入EHEC抗原LomW，EscC，LpfA1，或LpfA2和使用金纳米粒子交付可以引发强大的抗原特异性细胞和体液反应与减少EHEC在体内定植。此外，我们的体外机制研究进一步支持抗体介导的保护主要是通过抑制细菌粘附到肠上皮细胞上以及通过促进巨噬细胞摄取和杀伤来驱动的。重要性肠出血性大肠杆菌大肠杆菌O157：H7仍然是一种重要的人类病原体，目前还没有有效和安全的疫苗。我们在鉴定新型保护性抗原方面取得了突出进展，这些抗原已被纳入金纳米颗粒平台并用作疫苗。在这项研究中，我们已经改进了我们的疫苗配方，以纳入多种抗原，并进一步确定抗体介导的保护机制，包括一种促进巨噬细胞摄取的疫苗。我们进一步定义了我们的纳米疫苗制剂在粘膜表面引起的细胞介导的反应，这是与保护相关的另一种关键免疫机制。
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 remains a pathogen of significance and high consequence around the world. This outcome is due in part to the high economic impact associated with massive, contaminated product recalls, prevalence of the pathogen in carrier reservoirs, disease sequelae, and mortality associated with several outbreaks worldwide. Furthermore, the contraindication of antibiotic use for the treatment of EHEC-related infections makes this pathogen a primary candidate for the development of effective prophylactic vaccines. However, no vaccines are approved for human use, and many have failed to provide a high degree of efficacy or broad protection, thereby opening an avenue for the use of new technologies to produce a safe, effective, and protective vaccine. Building on our previous studies using reverse vaccinology-predicted antigens, we refine a formulation, evaluate new immunogenic antigens, and further expand our understanding about the mechanism of EHEC vaccine-mediated protection. In the current study, we exploit the use of the nanotechnology platform based on gold nanoparticles (AuNP), which can act as a scaffold for the delivery of various antigens. Our results demonstrate that a refined vaccine formulation incorporating EHEC antigen LomW, EscC, LpfA1, or LpfA2 and delivered using AuNPs can elicit robust antigen-specific cellular and humoral responses associated with reduced EHEC colonization in vivo. Furthermore, our in vitro mechanistic studies further support that antibody-mediated protection is primarily driven by inhibition of bacterial adherence onto intestinal epithelial cells and by promotion of macrophage uptake and killing. IMPORTANCE Enterohemorrhagic E. coli O157:H7 remains an important human pathogen that does not have an effective and safe vaccine available. We have made outstanding progress in the identification of novel protective antigens that have been incorporated into the gold nanoparticle platform and used as vaccines. In this study, we have refined our vaccine formulations to incorporate multiple antigens and further define the mechanism of antibody-mediated protection, including one vaccine that promotes macrophage uptake. We further define the cell-mediated responses elicited at the mucosal surface by our nanovaccine formulations, another key immune mechanism linked to protection.
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DOI：
10.1007/978-1-0716-0338-3_13
发表时间：
2020-01-01
期刊：
INNATE LYMPHOID CELLS
影响因子：
--
作者：
James, Olivia Jane;Vandereyken, Maud;Swamy, Mahima
通讯作者：
Swamy, Mahima
DOI：
10.1007/978-1-0716-0389-5_1
发表时间：
2020-01-01
期刊：
IMMUNOINFORMATICS, 3 EDITION
影响因子：
--
作者：
Kanampalliwar, Amol M.
通讯作者：
Kanampalliwar, Amol M.
影响因子：
3.7
作者：
Kaper JB;O'Brien AD
通讯作者：
O'Brien AD
影响因子：
5.5
作者：
Garcia-Angulo, Victor A.;Kalita, Anjana;Torres, Alfredo G.
通讯作者：
Torres, Alfredo G.
影响因子：
5
作者：
Staroverov SA;Volkov AA;Mezhenny PV;Domnitsky IY;Fomin AS;Kozlov SV;Dykman LA;Guliy OI
通讯作者：
Guliy OI