A conserved N protein nano‐vaccine of COVID‐19 exerts potent and cross‐reactive humoral and cellular immune responses in mice

Abstract As severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) mutates continually, the current vaccines are unable to provide sufficient protection. It is important to develop a broad‐spectrum vaccine with conserved antigens to prevent variant infection. Here we fused the SARS‐CoV‐2 N protein with Helicobacter pylori nonheme ferritin to construct a SARS‐CoV‐2 N‐Ferritin nanoparticle vaccine. Compared with the monomer N protein, the N‐Ferritin nanoparticles induced more lymph node dendritic cells in mice to trigger adoptive immunity. Following this, the N‐Ferritin elicited more robust and long‐lasting antibody responses, which had better cross‐reactivity with the SARS‐CoV N protein. It is also worth noting that higher levels of N‐specific IgG and IgA were distributed in the lungs of N‐Ferritin‐immunized mice. Furthermore, the N‐Ferritin nanoparticles also resulted higher proportion of interferon‐γ + CD8 + T cells, CD8 + Tcm cells, and T cells with cross‐reactivity in SARS‐CoV‐2, SARS‐CoV, and Middle East respiratory syndrome‐related coronavirus. The conserved N‐based nanoparticles could provide a promising vaccine developing strategy against SARS‐CoV‐2 variants and other coronaviruses.