A new vaccine strategy based on VLSs for use against SARS-CoV-2 variants: Evaluation of their immune effectiveness and investigation of the mechanism

Abstract A new lipid system broadening the capacity of antigen carriage, including mRNA and protein, is established, and an assembled virus-like-structure (VLS) encapsulated mRNA of S1 protein from XBB.1 and loaded S1 protein from omicron BA.1 on the surface is identified. This characterized VLS enables to specifically augment mRNA expression in human respiratory epithelial cells and macrophages via its loaded S1 protein on the surface interacting with ACE2 or DC-SIGN molecules of cells. It also archives effective mRNA expression in mouse dendritic cells (DCs) and macrophages via surface S1 protein binding to DC-SIGN molecules followed by the activation of DCs and macrophages in mice. The intensive antibody response against viral variants in Balb/c mice immunized by VLS was observed to be greater than those immunized by mRNA or protein vaccine alone, while ACE+/+ mice and hamsters immunized with VLS were observed to be more effective for restraining viral replication of the Omicron or Wuhan strain challenge. The mechanism of this robust immunity elicited by VLS was found being involved in the integrated effect of diverse signals from activated innate immunity to the adaptive immune system.