The immunologic dominance of an epitope within a rationally designed poly-epitope vaccine is influenced by multiple factors.

Jiayi Shu, Wei Shen, Haitao Liu, Yiqing Zhou, Jianhui Li, Yan Zhuang, Zhenghui Huang, Shigang Yin, Lubin Jiang, Yongtao Sun, Xia Jin, Jianqing Xu

Vaccine 2020 Mar 23

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CD4+ T cells are essential for inducing optimal CD8+ T cell and antibody-producing B cell responses and maintaining their long-term immunological memory. Therefore, CD4+ T cells are a critical component in HIV vaccine development. Due to enormous viral gene variation and significant human host genetic diversity, HIV vaccines may need to be custom-made for different countries. Previously, we designed a CD4+ T cell vaccine based on Chinese HIV isolates and HLA-DR alleles using bioinformatics tools and predicted that 20 epitopes could cover 98.1% of the Chinese population. In vivo testing of the poly-epitope antigen in mice only activated specific T cells for some epitopes. To elucidate the mechanism of the observed differential immunogenicity, we examined poly-epitope antigen processing and presentation using in vitro and in vivo analytical methods. Enzymatic digestion indicated that all 20 epitopes comprising the poly-epitope antigen could be liberated, but MHC II binding assays showed that neither binding affinity nor dissociation rate was associated with the magnitude of T cell immune responses elicited by each peptide epitope in vaccinated mice. Mass spectrometry analysis of MHC II-bound peptides suggested that the abundance of endogenously processed peptides bound to MHC II molecules was significantly associated with the relative immunodominance of these epitopes. These results provide a new rationale for improving the design and testing of poly-epitope vaccines for HIV and other diseases. Copyright © 2020 Elsevier Ltd. All rights reserved.

Citation

Jiayi Shu, Wei Shen, Haitao Liu, Yiqing Zhou, Jianhui Li, Yan Zhuang, Zhenghui Huang, Shigang Yin, Lubin Jiang, Yongtao Sun, Xia Jin, Jianqing Xu. The immunologic dominance of an epitope within a rationally designed poly-epitope vaccine is influenced by multiple factors. Vaccine. 2020 Mar 23;38(14):2913-2924