RBD conjugate vaccine with a built-in TLR1/2 agonist is highly immunogenic against SARS-CoV-2 and variants of concern
RBD conjugate vaccine with a built-in TLR1/2 agonist is highly immunogenic against SARS-CoV-2 and variants of concern
复制标题
内置 TLR1/2 激动剂的 RBD 结合疫苗对 SARS-CoV-2 和相关变体具有高度免疫原性
DOI：
10.1039/d1cc06520c
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发表时间：
2022
影响因子：
4.9
通讯作者：
Guo Jun
中科院分区：
文献类型：
--
作者：
Zhou Shi-Hao;Zhang Ru-Yan;Zhang Hai-Wei;Liu Yan-Ling;Wen Yu;Wang Jian;Li Yu-Ting;You Zi-Wei;Yin Xu-Guang;Qiu Hong;Gong Rui;Yang Guang-Fu;Guo Jun
2019年冠状病毒(新冠肺炎)大流行正在世界范围内造成严重影响，安全有效的疫苗和药物是抗击该疾病的最佳方法。SARS-CoV-2刺突蛋白的受体结合域(RBD)在与血管紧张素转换酶2(ACE2)受体的相互作用中起着关键作用，被认为是疫苗的重要靶点。在此，我们构建了佐剂-蛋白结合物Pam3CSK4-RBD作为候选疫苗，其中RBD的N端通过转氨基选择性氧化并与TLR1/2激动剂Pam3CSK4偶联。这说明Pam3CSK4的偶联显著增强了抗RBD抗体应答和细胞应答。此外，Pam3CSK4-RBD免疫组的血清有效地抑制了RBD与ACE2的结合，并保护细胞免受SARS-CoV-2和四个关注变异体(α、β、γ和Delta)的影响，表明这种佐剂策略可能是蛋白质疫苗开发的有效手段之一。
The coronavirus 2019 (COVID-19) pandemic is causing serious impacts in the world, and safe and effective vaccines and medicines are the best methods to combat the disease. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a key role in interacting with the angiotensin-converting enzyme 2 (ACE2) receptor, and is regarded as an important target of vaccines. Herein, we constructed the adjuvant–protein conjugate Pam3CSK4–RBD as a vaccine candidate, in which the N-terminal of the RBD was site-selectively oxidized by transamination and conjugated with the TLR1/2 agonist Pam3CSK4. This demonstrated that the conjugation of Pam3CSK4 significantly enhanced the anti-RBD antibody response and cellular response. In addition, sera from the Pam3CSK4-RBD immunized group efficiently inhibited the binding of the RBD to ACE2 and protected cells from SARS-CoV-2 and four variants of concern (alpha, beta, gamma and delta), indicating that this adjuvant strategy could be one of the effective means for protein vaccine development.