Engineering a Self-Navigated MnARK Nanovaccine for Inducing Potent Protective Immunity against Novel Coronavirus

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

Effective vaccines are vital to the 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, mice immunized with the MnARK vaccine immunized mice showed stronger neutralizing abilities against the infection of the pseudovirus (~270-fold) and live coronavirus (>8-fold) in vitro 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 DC cells, 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.