Influenza Virus-like Particle-Based Hybrid Vaccine Containing RBD Induces Immunity against Influenza and SARS-CoV-2 Viruses

Abstract

Several approaches have produced an effective vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since millions of people are exposed to influenza virus and SARS-CoV-2, it is of great interest to develop a two-in-one vaccine that will be able to protect against infection of both viruses. We have developed a hybrid vaccine for SARS-CoV-2 and influenza viruses using influenza virus-like particles (VLP) incorporated by protein transfer with glycosylphosphatidylinositol (GPI)-anchored SARS-CoV-2 RBD fused to GM-CSF as an adjuvant. GPI-RBD-GM-CSF fusion protein was expressed in CHO-S cells, purified and incorporated onto influenza VLPs to develop the hybrid vaccine. Our results show that the hybrid vaccine induced a strong antibody response and protected mice from both influenza virus and mouse-adapted SARS-CoV-2 challenges, with vaccinated mice having significantly lower lung viral titers compared to naive mice. These results suggest that a hybrid vaccine strategy is a promising approach for developing multivalent vaccines to prevent influenza A and SARS-CoV-2 infections.

Hemagglutinin virus-like particles incorporated with membrane-bound cytokine adjuvants provide protection against homologous and heterologous influenza virus challenge in aged mice

“…We incorporated affinity purified GPI-GM-CSF and GPI-IL-12 into HA-VLPs by protein transfer to prepare our VLP-GM-CSF-IL-12 (HA-VLP-Cyt) vaccine as described (Fig. 1 B) [ 21 ]. GPI-cytokine incorporation into HA-VLP was detected by flow cytometry analysis (Fig.…”

“…Vaccination with VLPs containing hemagglutinin (HA) from influenza A/California/2009 was shown to induce a more protective immune response in ferrets in comparison to a conventional inactivated virus vaccination [ 20 ]. Another advantage of VLPs is that it can be modified to display immunostimulatory cytokines as adjuvants to enhance the vaccine efficacy [ 21 , 22 ]. These features suggest that VLPs can be used as a potent vaccine platform to develop vaccines for influenza.…”

“…Our earlier studies have shown that incorporation of GPI-anchored GM-CSF into the HA-VLP lipid envelope improves anti-viral immunity after vaccination of young adult mice [ 21 , 22 ]. Here, influenza VLP vaccines that express HA from influenza A/PR8 virus (HA-VLP) were modified to display GPI-GM-CSF and GPI-IL-12 on the HA-VLP surface via protein transfer.…”

Respiratory Viruses and Virus-like Particle Vaccine Development: How Far Have We Advanced?

“…Glycosylphosphatidylinositol-anchored SARS-CoV-2 S RBD was fused to the GM-CSF adjuvant, and this was incorporated into influenza VLPs expressing the HA and M1 derived from influenza A/Puerto Rico/8/1934 (PR8). This mammalian cell-derived VLP vaccine conferred protection against both influenza and SARS-CoV-2 virus challenge infection in mice [ 141 ]. Incorporating cyclic GMP-AMP (cGAMP) into VLPs significantly increased the vaccine immunogenicity against multiple respiratory viruses.…”

From Co-Administration to Co-Formulation: The Race for New Vaccines against COVID-19 and Other Respiratory Viruses

“…More manufacturers can join this race, as many different co-formulated vaccines are still under preclinical development [ 14 , 15 , 16 , 17 , 18 ], including live-attenuated influenza virus (LAIV) vector-based vaccines [ 19 , 20 , 21 ]. Among the latter, the intranasal candidate developed by Beijing Wantai Biological Pharmacy Enterprise achieved poor immunogenicity in a phase 1/2 clinical trial [ 22 ].…”