Immunogenicity and protective efficacy of an influenza virus-like particle-based SARS-CoV-2 hybrid vaccine candidate in rhesus macaques

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus co-infections present a heightened COVID-19 disease and hospitalization cases. Here, we studied the immunogenicity and efficacy of an influenza-A/PR8 virus-like particle (FluVLP)-based hybrid vaccine candidate displaying GPI-anchored SARS-CoV-2 receptor binding domain fused to GM-CSF and GPI-anchored interleukin-12 (FluVLP-RBD) in rhesus macaques. Animals (n=4/group) received two doses of either FluVLP or FluVLP-RBD vaccine four weeks apart and were challenged with SARS-CoV-2 (WA1/2020) infection via intranasal and intratracheal routes. We determined vaccine-induced IgG and neutralizing antibody titers in serum and their association with viral replication in the lower and upper airways (lung, throat, and nose) and lung-associated pathologies. FluVLP-RBD vaccine induced a strong binding IgG in serum against multiple SARS-CoV-2 variants (WA1/2020, Delta and Omicron; BA.1). Both vaccines induced strong influenza A/PR8-specific IgG. Following the SARS-CoV-2 challenge, all four animals in the FluVLP-RBD group showed a profound control of virus replication in all three airway compartments as early as day 2 through day 10 (day of euthanasia). This level of viral control was not observed in the FluVLP group as 2-3 animals exhibited high virus replication in all three airway compartments. The protection in the FluVLP-RBD vaccinated group correlated positively with post challenge neutralizing antibody titer. These results demonstrated that a FluVLP-based hybrid SARS-CoV-2 vaccine induces strong antibody responses against influenza-A/PR8 and multiple SARS-CoV-2 RBD variants and protects from SARS-CoV-2 replication in multiple compartments in macaques. These findings provide important insights for developing multivalent vaccine strategies for respiratory viruses.