Delivery of SARS-CoV-2 spike and membrane genes in a single Baculoviral vector enhance the immune breadth against SARS-CoV-2 variants of concern.

Although the coronavirus pandemic has ended, new variants of concern (VOCs) continue to emerge. Therefore, novel vaccines targeting VOCs are highly warranted. We initially constructed three recombinant baculovirus-vectored vaccines (AcHERV-COVID19S) carrying the spike genes of the SARS-CoV-2 prototype, Delta, and Omicron BA.1 variants. However, the SARS-CoV-2 spike gene alone could not provide protection against multiple VOCs. To develop a universal vaccine, we constructed a recombinant baculovirus-vectored vaccine (AcHERV-COVID19 OmiM) by introducing the M gene, which is conserved among VOCs, as a secondary cellular immune antigen in addition to the S gene. AcHERV-COVID19 OmiM could provide higher protection against SARS-CoV-2 variants (prototype, Delta, BA.5 and XBB.1) compared with that of AcHERV-COVID19S. The membrane protein of SARS-CoV-2 synergizes with the S gene, thereby enhancing both humoral and cellular immunity against VOCs. Although AcHERV-COVID19 OmiM may not provide sterile protection against new variants, it may help reduce symptoms and curb viral transmission.