tetano
Editor, Senior Moderator
Clin Vaccine Immunol. 2014 Feb 12. [Epub ahead of print]
TLR7 agonist imiquimod in combination with influenza vaccine expedite and augment humoral immune responses against influenza A(H1N1)pdm09 infection in BALB/c mice.
Zhang AJ, Li C, To KK, Zhu HS, Lee AC, Li CG, Chan JF, **** IF, Yuen KY.
Author information
Abstract
Toll-like receptors (TLRs) of innate immune system are known targets for enhancing vaccine efficacy. We investigated whether imiquimod, a synthetic TLR7 agonist, when combined with influenza vaccine can expedite the immune response against influenza infection. BALB/c mice were immunized with monovalent A(H1N1)pdm09 vaccine combined with imiquimod (VCI) intraperitoneally prior to intranasal inoculation with a lethal dose of mouse-adapted A(H1N1)pdm09 virus. For mice immunized 3 days before infection, the survival rates were significantly higher in VCI group (60%, mean survival time[MST], 11 days) than the vaccine alone (30%, MST 8.8 days), imiquimod alone (5%, MST 8.4 days) and PBS (0%, MST 6.2 days)(P<0.01). For the VCI group, 45% and 35% of mice survived even when the mice were infected at 2 day or 1 day after immunization. Virus specific serum IgM, IgG, and neutralizing antibody appeared earlier with higher geometric mean titer in VCI group than control groups. The pulmonary viral load was significantly lower at all time-points post-infection for the VCI, vaccine alone or imiquimod alone groups than the PBS control group(P<0.05). The protection induced by VCI was specific for A(H1N1)pdm09 virus but not for A(H5N1) virus. Since imiquimod combined with RNase-treated vaccine is as protective as imiquimod combined with untreated vaccine, mechanisms other than TLR7 may operate in expediting and augmenting the immune protection. Moreover, increased mRNA expression of interferon-γ or IgG isotype switching which are markers of Th1 response induced by imiquimod, were not apparent in our mice model. The mechanisms of imiquimod-induced immune protection deserve further studies.
PMID:
24521786
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24521786
TLR7 agonist imiquimod in combination with influenza vaccine expedite and augment humoral immune responses against influenza A(H1N1)pdm09 infection in BALB/c mice.
Zhang AJ, Li C, To KK, Zhu HS, Lee AC, Li CG, Chan JF, **** IF, Yuen KY.
Author information
Abstract
Toll-like receptors (TLRs) of innate immune system are known targets for enhancing vaccine efficacy. We investigated whether imiquimod, a synthetic TLR7 agonist, when combined with influenza vaccine can expedite the immune response against influenza infection. BALB/c mice were immunized with monovalent A(H1N1)pdm09 vaccine combined with imiquimod (VCI) intraperitoneally prior to intranasal inoculation with a lethal dose of mouse-adapted A(H1N1)pdm09 virus. For mice immunized 3 days before infection, the survival rates were significantly higher in VCI group (60%, mean survival time[MST], 11 days) than the vaccine alone (30%, MST 8.8 days), imiquimod alone (5%, MST 8.4 days) and PBS (0%, MST 6.2 days)(P<0.01). For the VCI group, 45% and 35% of mice survived even when the mice were infected at 2 day or 1 day after immunization. Virus specific serum IgM, IgG, and neutralizing antibody appeared earlier with higher geometric mean titer in VCI group than control groups. The pulmonary viral load was significantly lower at all time-points post-infection for the VCI, vaccine alone or imiquimod alone groups than the PBS control group(P<0.05). The protection induced by VCI was specific for A(H1N1)pdm09 virus but not for A(H5N1) virus. Since imiquimod combined with RNase-treated vaccine is as protective as imiquimod combined with untreated vaccine, mechanisms other than TLR7 may operate in expediting and augmenting the immune protection. Moreover, increased mRNA expression of interferon-γ or IgG isotype switching which are markers of Th1 response induced by imiquimod, were not apparent in our mice model. The mechanisms of imiquimod-induced immune protection deserve further studies.
PMID:
24521786
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24521786