Severe Acute Respiratory Syndrome Coronavirus‐2 Spike Protein Nanogel as a Pro‐Antigen Strategy with Enhanced Protective Immune Responses

Chen, Long; Liu, Bo; Sun, Peng; Wang, Wenjun; Luo, Shiqiang; Zhang, Wenyuan; Yang, Yuanfan; Wang, Zihao; Lin, Jian; Chen, Peng R.

Prevention and intervention methods are urgently needed to curb the global pandemic of coronavirus disease‐19 caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). Herein, a general pro‐antigen strategy for subunit vaccine development based on the reversibly formulated receptor binding domain of SARS‐CoV‐2 spike protein (S‐RBD) is reported. Since the poor lymph node targeting and uptake of S‐RBD by antigen‐presenting cells prevent effective immune responses, S‐RBD protein is formulated into a reversible nanogel (S‐RBD‐NG), which serves as a pro‐antigen with enhanced lymph node targeting and dendritic cell and macrophage accumulation. Synchronized release of S‐RBD monomers from the internalized S‐RBD‐NG pro‐antigen triggers more potent immune responses in vivo. In addition, by optimizing the adjuvant used, the potency of S‐RBD‐NG is further improved, which may provide a generally applicable, safer, and more effective strategy for subunit vaccine development against SARS‐CoV‐2 as well as other viruses.