DNA immunization with in silico predicted T-cell epitopes protects against lethal SARS-CoV-2 infection in K18-hACE2 mice

Gry Persson; Katherine H Restori; Julie Hincheli Emdrup; Sophie Schussek; Michael Schantz Klausen; McKayla J Nicol; Bhuvana Katkere; Birgitte Rønø; Girish Kirimanjeswara; Anders Bundgaard Sørensen

doi:10.3389/fimmu.2023.1166546

DNA immunization with in silico predicted T-cell epitopes protects against lethal SARS-CoV-2 infection in K18-hACE2 mice

Front Immunol. 2023 Apr 11:14:1166546. doi: 10.3389/fimmu.2023.1166546. eCollection 2023.

Affiliations

¹ Evaxion Biotech A/S, Hoersholm, Denmark.
² Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA, United States.

Abstract

The global SARS-CoV-2 pandemic caused significant social and economic disruption worldwide, despite highly effective vaccines being developed at an unprecedented speed. Because the first licensed vaccines target only single B-cell antigens, antigenic drift could lead to loss of efficacy against emerging SARS-CoV-2 variants. Improving B-cell vaccines by including multiple T-cell epitopes could solve this problem. Here, we show that in silico predicted MHC class I/II ligands induce robust T-cell responses and protect against severe disease in genetically modified K18-hACE2/BL6 mice susceptible to SARS-CoV-2 infection.

Keywords: COVID-19; SARS-CoV-2; T-cell vaccine; machine learning; viral challenge model.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
COVID-19* / prevention & control
DNA
Epitopes, T-Lymphocyte
Immunization
Mice
SARS-CoV-2
Vaccines, DNA*

Substances

DNA
Epitopes, T-Lymphocyte
K-18 conjugate
Vaccines, DNA
ACE2 protein, human

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

GP, AS, JE, SS, MK, and BR were partially funded by The Innovation Fund Denmark (0174-00039B). GSK was support by the United State Department of Agriculture (#4771).