Preclinical development of a cross-protective β-SARS-CoV-2 virus-like particle vaccine adjuvanted with MF59

Whilst COVID vaccines proved to be effective in preventing severe COVID disease, they failed to control the emergence of variant viruses and antibody responses waned quickly. We report the findings of a recombinant β-SARS-CoV-2 variant virus-like particle (VLP) vaccine composed of the viral spike (S), membrane (M) and envelope (E) proteins produced in Vero cell factories. The β-SARS-CoV-2 VLP vaccine formulated with Addavax or MF59 produced strong antibody and CD4 + T cell responses and was protective in mice against pulmonary infection with Beta, Delta and Omicron BA.5 variant viruses. Multiplex RBD-ACE2 binding inhibition assay was performed as a surrogate virus neutralisation test and revealed immune sera from immunised mice produced low-titre broad-inhibitory anti-RBD-ACE2 antibodies (sNAb) to Alpha, Delta, Beta, Gamma, Mu, Omicron BA.1, BA.2, BA.5 and XBB1.5. However, microneutralisation assays did not show the presence of sNAb. The β-SARS-CoV-2 VLP is strongly immunogenic producing broad antibody and T cell responses and is protective against infection with SARS-CoV-2 variant viruses.