Yeast-expressed SARS-CoV recombinant receptor-binding domain (RBD219-N1) formulated with aluminum hydroxide induces protective immunity and reduces immune enhancement.
Yeast-expressed SARS-CoV recombinant receptor-binding domain (RBD219-N1) formulated with aluminum hydroxide induces protective immunity and reduces immune enhancement.
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DOI：
10.1016/j.vaccine.2020.09.061
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发表时间：
2020-11-03
期刊：
影响因子：
5.5
通讯作者：
Tseng CK
中科院分区：
文献类型：
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作者：
Chen WH;Tao X;Agrawal AS;Algaissi A;Peng BH;Pollet J;Strych U;Bottazzi ME;Hotez PJ;Lustigman S;Du L;Jiang S;Tseng CK
明矾上的sars冠状病毒RBD疫苗具有高中和效价和100%的存活率。明矾上的sars冠状病毒RBD疫苗可防止病毒攻击时肺细胞浸润。与由SARS-CoV S蛋白组成的疫苗相比，明矾上的SARS-CoV RBD疫苗大大减少了肺嗜酸性粒细胞。明矾上的sars冠状病毒RBD疫苗正在作为人类疫苗开发。我们开发了一种基于高产、酵母工程的SARS β冠状病毒（SARS- cov）刺突蛋白受体结合域（RBD219-N1）的严重急性呼吸综合征（SARS）亚单位重组蛋白候选疫苗。当与醛水凝胶®配制时，RBD219-N1诱导高水平的中和抗体，以对抗假型病毒和临床（小鼠适应）SARS-CoV分离物。在这里，我们报告用RBD219-N1/Alhydrogel®免疫的小鼠完全免受致命的SARS- cov攻击（死亡率为0%），而用Alhydrogel®配制的SARS S蛋白免疫的小鼠死亡率为~30%，阴性对照死亡率为100%。含有Alhydrogel®的RBD219-N1制剂在诱导特异性抗体和防止肺细胞浸润方面也优于S蛋白、无佐剂RBD和AddaVax （mf59样佐剂）配制的RBD。具体来说，RBD219-N1与Alhydrogel®比例为1:25的配方提供了高中和抗体滴度，100%的保护，无法检测到病毒载量，很少或没有嗜酸性粒细胞肺浸润。因此，正在考虑进一步开发针对SARS-CoV和可能出现的其他新出现和再出现的β - cov（如SARS-CoV-2）的疫苗配方。
A SARS-CoV RBD vaccine on alum provides high neutralizing titers and 100% survival. A SARS-CoV RBD vaccine on alum prevents pulmonary cellular infiltrates upon virus challenge. A SARS-CoV RBD vaccine on alum greatly reduces lung eosinophils compared to a vaccine comprised of the SARS-CoV S protein. The SARS-CoV RBD vaccine on alum is being developed as a human vaccine. We developed a severe acute respiratory syndrome (SARS) subunit recombinant protein vaccine candidate based on a high-yielding, yeast-engineered, receptor-binding domain (RBD219-N1) of the SARS beta-coronavirus (SARS-CoV) spike (S) protein. When formulated with Alhydrogel®, RBD219-N1 induced high levels of neutralizing antibodies against both pseudotyped virus and a clinical (mouse-adapted) isolate of SARS-CoV. Here, we report that mice immunized with RBD219-N1/Alhydrogel® were fully protected from lethal SARS-CoV challenge (0% mortality), compared to ~30% mortality in mice immunized with the SARS S protein formulated with Alhydrogel®, and 100% mortality in negative controls. An RBD219-N1 formulation with Alhydrogel® was also superior to the S protein, unadjuvanted RBD, and AddaVax (MF59-like adjuvant)-formulated RBD in inducing specific antibodies and preventing cellular infiltrates in the lungs upon SARS-CoV challenge. Specifically, a formulation with a 1:25 ratio of RBD219-N1 to Alhydrogel® provided high neutralizing antibody titers, 100% protection with non-detectable viral loads with minimal or no eosinophilic pulmonary infiltrates. As a result, this vaccine formulation is under consideration for further development against SARS-CoV and potentially other emerging and re-emerging beta-CoVs such as SARS-CoV-2.
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DOI：
10.1016/b978-0-12-804019-5.00013-x
发表时间：
2017-01-01
期刊：
IMMUNOPOTENTIATORS IN MODERN VACCINES, 2ND EDITION
影响因子：
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作者：
Kommareddy, S.;Singh, M.;O'Hagan, D. T.
通讯作者：
O'Hagan, D. T.
DOI：
10.1016/j.bbrc.2009.05.003
发表时间：
2009-07-10
影响因子：
3.1
作者：
Du, Lanying;Zhao, Guangyu;Li, Lin;He, Yuxian;Zhou, Yusen;Zheng, Bo-Jian;Jiang, Shibo
通讯作者：
Jiang, Shibo
影响因子：
2.2
作者：
Du, Lanying;Zhao, Guangyu;Jiang, Shibo
通讯作者：
Jiang, Shibo
影响因子：
3.7
作者：
Du, Lanying;Zhao, Guangyu;Chan, Chris C. S.;Sun, Shihui;Chen, Min;Liu, Zhonghua;Guo, Hongxiang;He, Yuxian;Zhou, Yusen;Zheng, Bo-Jian;Jiang, Shibo
通讯作者：
Jiang, Shibo
DOI：
10.1038/nrmicro2090
发表时间：
2009-03
期刊：
Nature reviews. Microbiology
影响因子：
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作者：
通讯作者：
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