Application of Humanized MHC Transgenic Mice in the Screening of HLA-Restricted T Cell Epitopes for Influenza Vaccines.

Background: Annual influenza epidemics pose a significant burden on the global healthcare system. The currently available vaccines mainly induce the production of neutralizing antibodies against hemagglutinin and neuraminidase, which are prone to antigenic variation, and this can reduce vaccine efficacy. Vaccines designed to target T cell epitopes can be potentially valuable. Considering the difficulties in obtaining clinical samples and the unique advantages of mice in disease-related research, a mouse model that can simulate human immune responses can be a superior alternative to peripheral blood mononuclear cells for epitope screening.

Methods: The T cell epitopes of the A/California/07/2009 (H1N1) virus were predicted and utilized to evaluate the cellular immune responses of HLA-A2/DR1 and HLA-A11/DR1 transgenic mice during epitope screening. The selected peptides were used to immunize these two groups of transgenic mice, followed by a viral challenge to assess their protective efficacy.

Results: The epitopes that were predicted and screened could stimulate cellular immune responses in HLA-A2/DR1 transgenic mice, HLA-A11/DR1 transgenic mice, and C57BL/6 mice. Moreover, the transgenic mice exhibited stronger ability to produce IFN-γ than that of the wild-type mice. Upon immunization and subjecting to viral challenge, the selected peptides exhibited protective effects against the influenza virus.

Conclusions: The HLA-A2/DR1 and HLA-A11/DR1 transgenic mouse models can be used for the direct screening and validation of influenza virus T cell epitopes, which is crucial for designing T cell epitope vaccines against influenza viruses. Further, this method can be applied in epitope screening and vaccine designing before the spread of other emerging and sudden infectious diseases, thereby supporting epidemic control.