tetano
Editor, Senior Moderator
Front Immunol. 2018 Oct 12;9:2370. doi: 10.3389/fimmu.2018.02370. eCollection 2018.
[h=1]Co-stimulation With TLR7 Agonist Imiquimod and Inactivated Influenza Virus Particles Promotes Mouse B Cell Activation, Differentiation, and Accelerated Antigen Specific Antibody Production.[/h] Li C[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], To KKW[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Zhang AJX[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Lee ACY[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Zhu H[SUP]5[/SUP], Mak WWN[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Hung IFN[SUP]5[/SUP], Yuen KY[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Current influenza vaccines have relatively low effectiveness, especially against antigenically drifted strains, the effectiveness is even lower in the elderly and immunosuppressed individuals. We have previously shown in a randomized clinical trial that the topical application of a toll-like receptor 7 agonist, imiquimod, just before intradermal influenza vaccine could expedite and augment antibody response, including to antigenically-drifted strains. However, the mechanism of this vaccine and imiquimod combination approach is poorly understood. Here, we demonstrated that imiquimod alone directly activated purified mouse peritoneal B cells. When combined with inactivated H1N1/415742Md influenza virus particle (VP) as vaccine, co-stimulation of mouse peritoneal B cells in vitro induced stronger activation, proliferation, and production of virus-antigen specific IgM and IgG. Intraperitoneal injection of a combination of VP and imiquimod (VCI) was associated with an increased number of activated B cells with enhanced expression of CD86 in the mesenteric draining lymph nodes (mesLN) and the spleen at 18 h after injection. Three days after immunization with VCI, mouse spleen showed significantly more IgM and IgG secreting cells upon in vitro re-stimulation with inactivated virus, mouse sera were detected with viral neutralizing antibody. Transfer of these spleen B cells to na?ve mice improved survival after lethal dose of H1N1/415742Md challenge. More importantly, the functional response of VCI-induced B cell activation was demonstrated by early challenge with a lethal dose of H1N1/415742Md influenza virus at 3 days after immunization. The spleen and mediastinal lymph nodes (mdLN) in mice immunized with VCI had germinal center formation, and significantly higher number of plasmablasts, plasma cells, and virus-antigen specific IgM and IgG secreting cells at only 3-4 days post virus challenge, compared with those of mice that have received imiquimod, inactivated virus alone or PBS. Serum virus-specific IgG2a, IgG2b, and IgG1 and bronchoalveolar lavage fluid (BALF) virus-specific IgA at 3 or 4 days post challenge were significantly higher in mice immunized with VCI, which had significantly reduced lung viral load and 100% survival. These findings suggested that imiquimod accelerates the vaccine-induced antibody production via inducing rapid differentiation of na?ve B cells into antigen-specific antibody producing cells.
[h=4]KEYWORDS:[/h] A(H1N1)pdm09; B cell; TLR7; imiquimod; inactivated influenza; mouse; peritoneal
PMID: 30369932 PMCID: PMC6194170 DOI: 10.3389/fimmu.2018.02370
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[h=1]Co-stimulation With TLR7 Agonist Imiquimod and Inactivated Influenza Virus Particles Promotes Mouse B Cell Activation, Differentiation, and Accelerated Antigen Specific Antibody Production.[/h] Li C[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], To KKW[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Zhang AJX[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Lee ACY[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Zhu H[SUP]5[/SUP], Mak WWN[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Hung IFN[SUP]5[/SUP], Yuen KY[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Current influenza vaccines have relatively low effectiveness, especially against antigenically drifted strains, the effectiveness is even lower in the elderly and immunosuppressed individuals. We have previously shown in a randomized clinical trial that the topical application of a toll-like receptor 7 agonist, imiquimod, just before intradermal influenza vaccine could expedite and augment antibody response, including to antigenically-drifted strains. However, the mechanism of this vaccine and imiquimod combination approach is poorly understood. Here, we demonstrated that imiquimod alone directly activated purified mouse peritoneal B cells. When combined with inactivated H1N1/415742Md influenza virus particle (VP) as vaccine, co-stimulation of mouse peritoneal B cells in vitro induced stronger activation, proliferation, and production of virus-antigen specific IgM and IgG. Intraperitoneal injection of a combination of VP and imiquimod (VCI) was associated with an increased number of activated B cells with enhanced expression of CD86 in the mesenteric draining lymph nodes (mesLN) and the spleen at 18 h after injection. Three days after immunization with VCI, mouse spleen showed significantly more IgM and IgG secreting cells upon in vitro re-stimulation with inactivated virus, mouse sera were detected with viral neutralizing antibody. Transfer of these spleen B cells to na?ve mice improved survival after lethal dose of H1N1/415742Md challenge. More importantly, the functional response of VCI-induced B cell activation was demonstrated by early challenge with a lethal dose of H1N1/415742Md influenza virus at 3 days after immunization. The spleen and mediastinal lymph nodes (mdLN) in mice immunized with VCI had germinal center formation, and significantly higher number of plasmablasts, plasma cells, and virus-antigen specific IgM and IgG secreting cells at only 3-4 days post virus challenge, compared with those of mice that have received imiquimod, inactivated virus alone or PBS. Serum virus-specific IgG2a, IgG2b, and IgG1 and bronchoalveolar lavage fluid (BALF) virus-specific IgA at 3 or 4 days post challenge were significantly higher in mice immunized with VCI, which had significantly reduced lung viral load and 100% survival. These findings suggested that imiquimod accelerates the vaccine-induced antibody production via inducing rapid differentiation of na?ve B cells into antigen-specific antibody producing cells.
[h=4]KEYWORDS:[/h] A(H1N1)pdm09; B cell; TLR7; imiquimod; inactivated influenza; mouse; peritoneal
PMID: 30369932 PMCID: PMC6194170 DOI: 10.3389/fimmu.2018.02370
Free full text