The immunologic dominance of an epitope within a rationally designed poly-epitope vaccine is influenced by multiple factors |
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| Affiliation: | 1. Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China;2. Viral Disease and Vaccine Translational Research Unit, Institut Pasteur of Shanghai, Chinese Academy of Sciences, B507 Life Science Research Building, 320 Yueyang Road, Shanghai 200031, China;3. School of Biotechnology and Food Engineering, Changshu Institute of Technology, Changshu, Jiangsu 215500, China;4. Department of Infectious Diseases, Tangdu Hospital, Air Force Medical University of PLA, 1 Xinsi Road, Xi''an, Shanxi 710038, China;5. Unit of Human Parasite Molecular and Cell Biology, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China;1. Center of Pathogen Biology and Immunology, Department of Microbiology and Immunology, Shantou University Medical College, Shantou 505041, Guangdong, China;2. Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou 505041, Guangdong, China;3. Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha 410011, China;1. Schaller Research Group at the University of Heidelberg and the DKFZ, Heidelberg, Germany;2. Department of Infectious Diseases, Virology, University of Heidelberg, Heidelberg, Germany;3. Bioquant, CellNetWorks, University of Heidelberg, Heidelberg, Germany;4. MRC, University of Glasgow Centre for Virus Research, Glasgow, Scotland, UK;1. Department of Morphology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil;2. School of Medicine, Postgraduate Program in Health Sciences: Infectology in Tropical Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais 30130-100, Brazil;3. René Rachou Research Center, FIOCRUZ, Belo Horizonte, Minas Gerais 30190-002, Brazil;4. Department of Molecular and Cellular Biology, Federal University of Paraíba, João Pessoa, Paraíba, Brazil;5. National Institute of Science and Technology on Tropical Diseases – INCT-DT, Salvador, Bahia, Brazil |
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| Abstract: | IntroductionCD4+ 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.MethodsPreviously, 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.ResultsEnzymatic 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.ConclusionThese results provide a new rationale for improving the design and testing of poly-epitope vaccines for HIV and other diseases. |
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| Keywords: | HIV Epitope-based vaccine Immunodominance |
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