Vaccine-induced antigen-specific regulatory T cells attenuate the antiviral immunity against acute influenza virus infection
Journal
Mucosal Immunology
Journal Volume
11
Journal Issue
4
Pages
1239-1253
Date Issued
2018
Author(s)
Lin, Pin-Hung
Wong, Weng-In
Wang, Yi-Lan
Hsieh, Meng-Ping
Liang, Chieh-Yu
Jui, Sung-Hsiang
Wu, Fang-Yi
Abstract
Peptide-based T cell vaccines targeting the conserved epitopes of influenza virus can provide cross-protection against distantly related strains, but they are generally not immunogenic. Foreign antigen-specific regulatory T (Treg) cells are induced under subimmunogenic conditions peripherally, although their development and role in vaccine-mediated antiviral immunity is unclear. Here, we demonstrated primary vaccination with peptides alone significantly induced antigen-specific Foxp3+ Treg cells, which were further expanded by repeated vaccination with unadjuvanted peptides. Certain adjuvants, including CpG, suppressed the induction and expansion of antigen-specific Treg cells by peptide vaccination. Interestingly, secondary influenza virus infection significantly increased the frequency of preexisting antigen-specific Treg cells, although primary infection barely induced them. Importantly, specific depletion of vaccine-induced antigen-specific Treg cells promoted influenza viral clearance, indicating their inhibitory role in vivo. Immunization with CpG-adjuvanted peptides by the subcutaneous prime-intranasal-boost strategy restricted the recruitment and accumulation of antigen-specific Treg cells in lung, and stimulated robust T cell immunity. Finally, subcutaneous prime-intranasal-boost immunization with CpG-adjuvanted peptides or whole-inactivated influenza vaccines protected mice from heterosubtypic influenza virus infection. In conclusion, antigen-specific Treg cells induced by peptide vaccines attenuate the antiviral immunity against influenza virus infection. CpG-adjuvanted peptide vaccines provide heterosubtypic influenza protection probably by inhibiting Treg development and enhancing T cell immunity. ? 2018 Society for Mucosal Immunology.
SDGs
Other Subjects
influenza vaccine; transcription factor FOXP3; virus antigen; epitope; immunological adjuvant; influenza vaccine; oligodeoxyribonucleotide; subunit vaccine; virus antigen; animal experiment; animal model; animal tissue; antigen specificity; Article; cellular immunity; controlled study; in vivo study; infant; influenza; influenza vaccination; mouse; nonhuman; priority journal; regulatory T lymphocyte; viral clearance; virus attenuation; virus immunity; acute disease; animal; C57BL mouse; human; immunological memory; immunology; immunosuppressive treatment; influenza; lymphocyte activation; Orthomyxoviridae; orthomyxovirus infection; physiology; regulatory T lymphocyte; secondary immunization; transgenic mouse; Acute Disease; Adjuvants, Immunologic; Animals; Antigens, Viral; Epitopes, T-Lymphocyte; Humans; Immunization, Secondary; Immunologic Memory; Immunosuppression; Influenza Vaccines; Influenza, Human; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Transgenic; Oligodeoxyribonucleotides; Orthomyxoviridae; Orthomyxoviridae Infections; T-Lymphocytes, Regulatory; Vaccines, Subunit
Publisher
Nature Publishing Group
Type
journal article