SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung.
SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung.
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DOI：
10.1038/s41467-021-23942-y
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发表时间：
2021-06-11
影响因子：
16.6
通讯作者：
Amara RR
中科院分区：
文献类型：
--
作者：
Routhu NK;Cheedarla N;Bollimpelli VS;Gangadhara S;Edara VV;Lai L;Sahoo A;Shiferaw A;Styles TM;Floyd K;Fischinger S;Atyeo C;Shin SA;Gumber S;Kirejczyk S;Dinnon KH 3rd;Shi PY;Menachery VD;Tomai M;Fox CB;Alter G;Vanderford TH;Gralinski L;Suthar MS;Amara RR
因此，迫切需要开发能够诱导对SARS-CoV-2产生强大而持久的保护性免疫的疫苗。抗原的多聚体展示与强佐剂相结合可以增强抗体反应的效力和寿命。刺突蛋白的受体结合域(RBD)是中和抗体的主要靶点。在这里，我们开发了一种RBD的三聚体形式，并表明它诱导了针对活病毒的强大中和抗体反应，具有多种效应器功能，并在小鼠和恒河猴身上提供了对SARS-CoV-2攻击的保护。与低至1μg抗原剂量的单体相比，三聚体可诱导更高的中和抗体效价。在小鼠中，用TLR7/8激动剂配方明胶-3M-052佐剂该蛋白可诱导比明胶高100倍的中和抗体效价和更好的抗感染保护。SARS-CoV-2感染会导致肺部固有细胞和病理的显著丧失，而疫苗接种可以保护固有细胞和肺部病理的变化。这些结果表明，RBD三聚体蛋白是一种适合SARS-CoV-2疫苗的候选蛋白。需要有效的SARS-CoV-2疫苗。在这里，作者证明了SARS-CoV-2刺突的受体结合域的三聚体形式与明胶-3M-052佐剂，保护非人类灵长类动物免受疾病和抑制感染。
There is a great need for the development of vaccines that induce potent and long-lasting protective immunity against SARS-CoV-2. Multimeric display of the antigen combined with potent adjuvant can enhance the potency and longevity of the antibody response. The receptor binding domain (RBD) of the spike protein is a primary target of neutralizing antibodies. Here, we developed a trimeric form of the RBD and show that it induces a potent neutralizing antibody response against live virus with diverse effector functions and provides protection against SARS-CoV-2 challenge in mice and rhesus macaques. The trimeric form induces higher neutralizing antibody titer compared to monomer with as low as 1μg antigen dose. In mice, adjuvanting the protein with a TLR7/8 agonist formulation alum-3M-052 induces 100-fold higher neutralizing antibody titer and superior protection from infection compared to alum. SARS-CoV-2 infection causes significant loss of innate cells and pathology in the lung, and vaccination protects from changes in innate cells and lung pathology. These results demonstrate RBD trimer protein as a suitable candidate for vaccine against SARS-CoV-2. Efficient vaccines for SARS-CoV-2 are needed. Here, the authors show that a trimeric form of the receptor-binding domain of SARS-CoV-2 spike adjuvanted with alum-3M-052 protects non-human primates from disease and inhibits infection.
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影响因子：
5.5
作者：
Guebre-Xabier M;Patel N;Tian JH;Zhou B;Maciejewski S;Lam K;Portnoff AD;Massare MJ;Frieman MB;Piedra PA;Ellingsworth L;Glenn G;Smith G
通讯作者：
Smith G
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5.4
作者：
Kasturi, Sudhir Pai;Kozlowski, Pamela A.;Pulendran, Bali
通讯作者：
Pulendran, Bali
影响因子：
2.2
作者：
Karsten, Christina B.;Mehta, Nickita;Alter, Galit
通讯作者：
Alter, Galit
影响因子：
158.5
作者：
Keech, Cheryl;Albert, Gary;Glenn, Gregory M.
通讯作者：
Glenn, Gregory M.
影响因子：
17.1
作者：
Kang, Yin-Feng;Sun, Cong;Zeng, Mu-Sheng
通讯作者：
Zeng, Mu-Sheng