tetano
Editor, Senior Moderator
Mucosal Immunol. 2018 Feb 21. doi: 10.1038/s41385-018-0004-9. [Epub ahead of print]
[h=1]Vaccine-induced antigen-specific regulatory T cells attenuate the antiviral immunity against acute influenza virus infection.[/h] Lin PH[SUP]1[/SUP], Wong WI[SUP]1[/SUP], Wang YL[SUP]1[/SUP], Hsieh MP[SUP]1[/SUP], Lu CW[SUP]1[/SUP], Liang CY[SUP]1[/SUP], Jui SH[SUP]1[/SUP], Wu FY[SUP]1[/SUP], Chen PJ[SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Yang HC[SUP]5,[/SUP][SUP]6,[/SUP][SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]+[/SUP] 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.
PMID: 29467445 DOI: 10.1038/s41385-018-0004-9
[h=1]Vaccine-induced antigen-specific regulatory T cells attenuate the antiviral immunity against acute influenza virus infection.[/h] Lin PH[SUP]1[/SUP], Wong WI[SUP]1[/SUP], Wang YL[SUP]1[/SUP], Hsieh MP[SUP]1[/SUP], Lu CW[SUP]1[/SUP], Liang CY[SUP]1[/SUP], Jui SH[SUP]1[/SUP], Wu FY[SUP]1[/SUP], Chen PJ[SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Yang HC[SUP]5,[/SUP][SUP]6,[/SUP][SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]+[/SUP] 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.
PMID: 29467445 DOI: 10.1038/s41385-018-0004-9