# Humanized Major Histocompatibility Complex Transgenic Mouse Model Can Play a Potent Role in SARS-CoV-2 Human Leukocyte Antigen-Restricted T Cell Epitope Screening

## TL;DR

This study shows that HLA-A11/DR1 transgenic mice can generate T cell responses to SARS-CoV-2 vaccines, making them useful for epitope screening without relying on human blood samples.

## Contribution

The study demonstrates that HLA-A11/DR1 mice can replace human PBMCs for T cell epitope screening, enabling faster vaccine development.

## Key findings

- HLA-A11/DR1 mice showed no severe pathogenic effects after SARS-CoV-2 infection.
- HLA-A11/DR1 mice produced specific IgG antibodies and IFN-γ after inactivated virus immunization.
- HLA-A11/DR1 mice can generate cellular immune responses suitable for epitope screening.

## Abstract

Background: COVID-19, caused by SARS-CoV-2, poses a significant threat to human health. Vaccines designed for T-cell epitopes play an important role in eliminating the virus. However, T cell epitope screening often requires the use of a large number of peripheral blood mononuclear cells (PBMCs) from infected or convalescent patients, and if MHC humanized mice can be used for epitope screening, they will not have to wait for enough PBMCs to be available to screen for epitopes, thus buying time for epitope confirmation and vaccine design. Methods: In this study, we used SARS-CoV-2 BA.5 to infect HLA-A11/DR1, C57BL/6, hACE2 mice, and detected body weight changes, viral load, and pathological changes after infection. Fourteen days after the HLA-A11/DR1 and C57BL/6 mice were immunized against inactivated viruses, IgG antibodies were detected in mouse serum using ELISA, and IFN-γ produced by peptide stimulation of splenocytes was detected by ELISpot. Results: There is no obvious pathogenic phenotype of SARS-CoV-2 infection in HLA-A11/DR1 mice. Specific IgG antibodies were detected in serum after immunization of inactivated virus in both HLA-A11/DR1 and C57BL/6 mice, but specific IFN-γ was detected in splenocytes of HLA-A11/DR1 mice. Conclusions: Although HLA-A11/DR1 mice are unable to replicate the virus effectively in vivo, they are able to generate cellular immune responses after immunization inactivated viruses. Therefore, it can be used as a tool to substitute for human PBMCs in epitope screening, thus shortening the timeliness of T cell epitope screening and obtaining the immunogenicity information of new epitopes in a timely manner.