A universal bacteriophage T4 nanoparticle platform to design multiplex SARS-CoV-2 vaccine candidates by CRISPR engineering.
A universal bacteriophage T4 nanoparticle platform to design multiplex SARS-CoV-2 vaccine candidates by CRISPR engineering.
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DOI：
10.1126/sciadv.abh1547
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发表时间：
2021-09-10
期刊：
影响因子：
13.6
通讯作者：
Rao VB
中科院分区：
文献类型：
--
作者：
Zhu J;Ananthaswamy N;Jain S;Batra H;Tang WC;Lewry DA;Richards ML;David SA;Kilgore PB;Sha J;Drelich A;Tseng CK;Chopra AK;Rao VB
CRISPR工程化的噬菌体T4-COVID疫苗提供多种SARS-CoV-2抗原，以提供更广泛的保护。迫切需要一个能够迅速产生多种候选疫苗的“通用”平台来控制流行病。我们以SARS冠状病毒2为模型，通过噬菌体T4的CRISPR工程构建了这样一个平台。通过将各种病毒组分掺入噬菌体纳米颗粒结构的适当隔室中来工程化疫苗候选物的管道。这些包括基因组中可表达的刺突基因，作为表面装饰的刺突和包膜表位，以及包装核心中的核衣壳蛋白。在动物模型中发现用刺突三聚体修饰的噬菌体是最有效的疫苗候选物。在没有任何佐剂的情况下，该疫苗刺激了强大的免疫应答，T辅助细胞1（TH 1）和TH 2免疫球蛋白G亚类，阻断了病毒-受体相互作用，中和了病毒感染，并赋予了针对病毒攻击的完全保护。这种新的纳米疫苗设计框架可能允许快速部署有效的无杀虫剂噬菌体疫苗，以对抗未来出现的任何病原体。
A CRISPR-engineered bacteriophage T4-COVID vaccine delivers multiple SARS-CoV-2 antigens for potential broader protection. A “universal” platform that can rapidly generate multiplex vaccine candidates is critically needed to control pandemics. Using the severe acute respiratory syndrome coronavirus 2 as a model, we have developed such a platform by CRISPR engineering of bacteriophage T4. A pipeline of vaccine candidates was engineered by incorporating various viral components into appropriate compartments of phage nanoparticle structure. These include expressible spike genes in genome, spike and envelope epitopes as surface decorations, and nucleocapsid proteins in packaged core. Phage decorated with spike trimers was found to be the most potent vaccine candidate in animal models. Without any adjuvant, this vaccine stimulated robust immune responses, both T helper cell 1 (TH1) and TH2 immunoglobulin G subclasses, blocked virus-receptor interactions, neutralized viral infection, and conferred complete protection against viral challenge. This new nanovaccine design framework might allow the rapid deployment of effective adjuvant-free phage-based vaccines against any emerging pathogen in the future.
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影响因子：
56.9
作者：
Hsieh, Ching-Lin;Goldsmith, Jory A.;McLellan, Jason S.
通讯作者：
McLellan, Jason S.
DOI：
10.1073/pnas.0400444101
发表时间：
2004-04-20
影响因子：
11.1
作者：
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DOI：
10.1073/pnas.1305923110
发表时间：
2013-06-25
影响因子：
11.1
作者：
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通讯作者：
Rohwer, Forest
影响因子：
56.9
作者：
Jordan, MB;Mills, DM;Cambier, JC
通讯作者：
Cambier, JC