Engineering a self-navigated MnARK nanovaccine for inducing potent protective immunity against novel coronavirus

Yaling Wang; Yuping Xie; Jia Luo; Mengyu Guo; Xuhao Hu; Xi Chen; Ziwei Chen; Xinyi Lu; Lichun Mao; Kai Zhang; Liangnian Wei; Yunfei Ma; Ruixin Wang; Jia Zhou; Chunyan He; Yufang Zhang; Ye Zhang; Sisi Chen; Lijuan Shen; Yun Chen; Nasha Qiu; Ying Liu; Yanyan Cui; Guoyang Liao; Ye Liu; Chunying Chen

doi:10.1016/j.nantod.2021.101139

Engineering a self-navigated MnARK nanovaccine for inducing potent protective immunity against novel coronavirus

Nano Today. 2021 Jun:38:101139. doi: 10.1016/j.nantod.2021.101139. Epub 2021 Mar 19.

Authors

Yaling Wang^{1

2}, Yuping Xie³, Jia Luo³, Mengyu Guo¹, Xuhao Hu^{1

4}, Xi Chen^{1

5}, Ziwei Chen^{1

4}, Xinyi Lu^{1

4}, Lichun Mao^{1

4}, Kai Zhang⁶, Liangnian Wei^{3

7}, Yunfei Ma³, Ruixin Wang³, Jia Zhou^{3

8}, Chunyan He³, Yufang Zhang³, Ye Zhang³, Sisi Chen³, Lijuan Shen⁸, Yun Chen⁷, Nasha Qiu¹, Ying Liu¹, Yanyan Cui⁹, Guoyang Liao³, Ye Liu³, Chunying Chen^{1

4

2

10}

Affiliations

¹ 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.
² GBA National Institute for Nanotechnology Innovation, Guangdong 510700, China.
³ Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650000, China.
⁴ University of Chinese Academy of Sciences, Beijing 100049, China.
⁵ School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
⁶ Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
⁷ Department of Immunology, Key Laboratory of Immune Microenvironment and Disease, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
⁸ Department of Pathology, School of Basic Medical Science, Kunming Medical University, Kunming, Yunnan 650500, China.
⁹ Beijing Engineering Research Center of Mixed Reality and Advanced Display, School of Optoelectronics, Beijing Institute of Technology, Beijing 100081, China.
¹⁰ Research Unit of Nanoscience and Technology, Chinese Academy of Medical Sciences, Beijing 100021, China.

Abstract

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) 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 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.