Viral codon optimization on SARS‐CoV‐2 Spike boosts immunity in the development of COVID‐19 mRNA vaccines

Abstract

AbstractLife‐long persistent herpesviruses carry “trans‐inducers” to overcome the unusual codon usage of their glycoproteins for efficient expression. Strikingly, this “trans‐inducibility” can be achieved by simply changing the codon‐usage of acute virus glycoproteins to that of persistent herpesvirus glycoproteins with herpesviral trans‐inducer. Here, we apply the “persistent viral codon‐usage‐trans‐inducer” principle to SARS‐CoV‐2 Spike mRNA vaccine platform, in which the codon‐usage of Spike is changed to that of Herpes Simplex Virus‐1 (HSV‐1) glycoprotein B (gB) with its “trans‐inducer” ICP27. The HSVgB‐ICP27‐codon‐optimized Spike mRNA vaccine induced markedly high antigen expression and stability, total IgG, neutralizing antibody, and T cell response, ultimately enhancing protection against lethal SARS‐CoV‐2 challenge. Moreover, the HSVgB‐ codon‐optimized Delta (B.1.617.2) strain Spike mRNA vaccine provided significant enhancements in antigen expression and long‐term protection against SARS‐CoV‐2 challenge. Thus, we report a novel persistent viral codon‐usage‐trans‐inducer mRNA vaccine platform for enhanced antigen expression and long‐term protection against lethal viral infection.