Intranasal Immunization with a Proteosome-Adjuvanted SARS-CoV2 Spike Protein-Based Vaccine is Immunogenic and Efficacious in Mice & Hamsters

Abstract

With the persistence of the SARS-CoV-2 pandemic and the emergence of novel variants, the development of novel vaccine formulations with enhanced immunogenicity profiles could help reduce disease burden in the future. Intranasally delivered vaccines offer a new modality to prevent SARS-CoV-2 infections through the induction of protective immune responses at the mucosal surface where viral entry occurs. Herein, we evaluated a novel protein subunit vaccine formulation containing a resistin-trimerized prefusion Spike antigen (SmT1v3) and a proteosome-based mucosal adjuvant (BDX301) formulated to enable intranasal immunization. In mice, the formulation induced robust antigen-specific IgG and IgA titers, in the blood and lungs, respectively. In addition, the formulations were highly efficacious in a hamster challenge model, reducing viral load and body weight loss. In both models, the serum antibodies had strong neutralizing activity, preventing the cellular binding of the viral Spike protein based on the ancestral reference strain, the Beta (B.1.351) and Delta (B.1.617.2) variants of concern. As such, this intranasal vaccine formulation warrants further development as a novel SARS-CoV-2 vaccine.

A CHO stable pool production platform for rapid clinical development of trimeric SARS‐CoV‐2 spike subunit vaccine antigens

“…In response to the COVID-19 pandemic, an important focus of our research has been the production of recombinant SARS-CoV-2 spike proteins in CHO cells. These proteins, specifically soluble, trimeric, prefusion-stabilized spike ectodomain constructs (Stuible et al, 2021), have been investigated as candidate vaccine antigens and also as reagents for serosurveillance studies (Akache et al, 2021(Akache et al, , 2022Chisanga et al, 2022;Colwill et al, 2022;Rudi et al, 2022;Stark et al, 2022;Stocks et al, 2021). With the frequent emergence of new variants, we have had the opportunity to generate dozens of spike-expressing CHO pools over the last 2 years, which has allowed us to appreciate better the performance and robustness of this expression platform.…”