Bivalent virus like particle (VLP)-based delivery of SARS-CoV-2 spike RBD-GM-CSF fusion protein induces durable and protective response

Several approaches have produced an effective vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the durability and efficacy of the immune response against SARS-CoV-2 in aged individuals is limited. Our objective is to develop a vaccine using influenza virus-like particles (VLPs) by incorporating GPI-RBD-GM-CSF fusion protein and GPI-IL-12 by protein transfer and demonstrate its efficacy and durability against influenza and SARS-CoV-2 viruses.

We have developed a bivalent VLP vaccine for influenza and SARS-CoV-2 using VLP incorporated with glycosylphosphatidylinositol (GPI)-anchored Spike RBD of SARS-CoV-2 fused to GM-CSF as an adjuvant. GPI-anchored fusion protein of GM-CSF and the SARS-CoV-2 S1 RBD was incorporated into influenza VLPs by protein transfer to make a bivalent VLP vaccine. The efficacy of the bivalent VLP vaccine was tested in both young and aged mice.

Our results show that the bivalent VLP vaccine induced a strong antibody response and protected the mice from both influenza virus and mouse-adapted SARS-CoV-2 challenges, with vaccinated mice having less body weight loss and significantly lower lung viral titers compared to control mice. The anti-viral immunity is long lasting and protective in aged mice immunized either when they are young and allowed to age or vaccinated when they are old prior to virus challenge.

The results suggest that the bivalent VLP vaccine is a promising candidate for preventing influenza A and SARS-CoV-2 infections.

Funding:

This work was supported by NIH/NIAID (SBIR Contract# 75N93019C00017 Amendment to Pack/Ramachandiran), and Intel Corporation for the Intel COVID-19 Global Technology Response Initiative grant.