Wang Yaling, Xie Yuping, Luo Jia, Guo Mengyu, Hu Xuhao, Chen Xi, Chen Ziwei, Lu Xinyi, Mao Lichun, Zhang Kai, Wei Liangnian, Ma Yunfei, Wang Ruixin, Zhou Jia, He Chunyan, Zhang Yufang, Zhang Ye, Chen Sisi, Shen Lijuan, Chen Yun, Qiu Nasha, Liu Ying, Cui Yanyan, Liao Guoyang, Liu Ye, Chen Chunying
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Chinese Academy of Sciences (CAS), Beijing 100190, China.
GBA National Institute for Nanotechnology Innovation, Guangdong 510700, China.
Nano Today. 2021 Jun;38:101139. doi: 10.1016/j.nantod.2021.101139. Epub 2021 Mar 19.
Effective vaccines are vital to fight against the COVID-19 global pandemic. As a critical component of a subunit vaccine, the adjuvant is responsible for strengthening the antigen-induced immune responses. Here, we present a new nanovaccine that comprising the Receptor-Binding Domain (RBD) of spike protein and the manganese nanoadjuvant (MnARK), which induces humoral and cellular responses. Notably, even at a 5-fold lower antigen dose and with fewer injections, the MnARK vaccine immunized mice showed stronger neutralizing abilities against the infection of the pseudovirus (~270-fold) and live coronavirus (>8-fold) than that of Alum-adsorbed RBD vaccine (Alu-RBD). Furthermore, we found that the effective co-delivery of RBD antigen and MnARK to lymph nodes (LNs) elicited an increased cellular internalization and the activation of immune cells, including DCs, CD4 and CD8 T lymphocytes. Our findings highlight the importance of MnARK adjuvant in the design of novel coronavirus vaccines and provide a rationale strategy to design protective vaccines through promoting cellular internalization and the activation of immune-related pathways.
有效的疫苗对于抗击新冠全球大流行至关重要。作为亚单位疫苗的关键组成部分，佐剂负责增强抗原诱导的免疫反应。在此，我们展示了一种新型纳米疫苗，其包含刺突蛋白的受体结合结构域（RBD）和锰纳米佐剂（MnARK），可诱导体液和细胞反应。值得注意的是，即使抗原剂量降低5倍且注射次数减少，用MnARK疫苗免疫的小鼠对伪病毒（约270倍）和活冠状病毒（>8倍）感染的中和能力仍比铝吸附RBD疫苗（Alu-RBD）更强。此外，我们发现RBD抗原和MnARK有效共递送至淋巴结（LNs）可引起细胞内化增加以及免疫细胞（包括树突状细胞、CD4和CD8 T淋巴细胞）的激活。我们的研究结果突出了MnARK佐剂在新型冠状病毒疫苗设计中的重要性，并提供了一种通过促进细胞内化和激活免疫相关途径来设计保护性疫苗的合理策略。
