Construction and immunogenicity of recombinant Lactiplantibacillus plantarum vaccine candidate expressing SARS-CoV-2 Omicron S1 protein

The current intramuscular SARS-CoV-2 vaccine failed to prevent variant strain outbreaks due to its inadequate stimulation of mucosal immunity. Therefore, nasal immunization is emerging as a promising alternative approach. In the present research, we have effectively created a mucosal vaccine candidate, designated rLP18:S1, which is intended to express the S1 protein of the Omicron variant (B.1.1.529). By inserting lipid-anchored signal peptide sequences, it efficiently displayed the Omicron S1 protein on the surface of Lactiplantibacillus plantarum . Notably, the recombinant protein from rLP18:S1 exhibits superior antigenicity and stability. We immunized mice nasally with rLP18:S1, inducing a robust antigen-specific mucosal immune response against Omicron virus infection. These results hold promise for the preclinical and clinical development of the Omicron SARS-CoV-2 vaccine. • Successful development of a mucosal vaccine against the Omicron variant of SARS-CoV-2. • Efficient display of Omicron S1 protein on Lactiplantibacillus plantarum . • Intranasal rLP18:S1 vaccination-induced immune response against Omicron virus.