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

Chih-Jen Lai; Dokyun Kim; Seokmin Kang; Kun Li; Inho Cha; Akimi Sasaki; Jose Porras; Tian Xia; Jae U Jung

doi:10.1002/jmv.29183

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

J Med Virol. 2023 Jan;95(10):e29183. doi: 10.1002/jmv.29183.

Authors

Chih-Jen Lai^{1

2}, Dokyun Kim^{1

2}, Seokmin Kang^{1

2}, Kun Li³, Inho Cha^{1

4}, Akimi Sasaki^{1

2}, Jose Porras³, Tian Xia^{1

2}, Jae U Jung^{1

2}

Affiliations

¹ Department of Cancer Biology and Infection Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
² Global Center for Pathogen Research and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
³ Florida Research and Innovation Center, Cleveland Clinic, Port St. Lucie, Florida, USA.
⁴ Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

PMID: 37861466
DOI: 10.1002/jmv.29183

Abstract

Life-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.

Keywords: Delta strain; Herpes Simplex Virus-1 (HSV-1) glycoprotein B (gB); ICP27; SARS-CoV-2; mRNA vaccine.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines* / genetics
COVID-19 Vaccines* / immunology
COVID-19* / genetics
COVID-19* / immunology
COVID-19* / prevention & control
Codon* / genetics
Codon* / immunology
Glycoproteins
Humans
SARS-CoV-2 / genetics
Spike Glycoprotein, Coronavirus* / genetics
Spike Glycoprotein, Coronavirus* / immunology
Viral Vaccines

Substances

Antibodies, Neutralizing
Antibodies, Viral
Codon
COVID-19 Vaccines
Glycoproteins
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
Viral Vaccines

Supplementary concepts

SARS-CoV-2 variants