File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Toll-like receptor 7 agonist imiquimod in combination with influenza vaccine expedites and augments humoral immune responses against influenza A(H1N1)pdm09 virus infection in BALB/c mice

TitleToll-like receptor 7 agonist imiquimod in combination with influenza vaccine expedites and augments humoral immune responses against influenza A(H1N1)pdm09 virus infection in BALB/c mice
Authors
Issue Date2014
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://cdli.asm.org/
Citation
Clinical and vaccine immunology, 2014, v. 21 n. 4, p. 570-579 How to Cite?
AbstractToll-like receptors (TLRs) of the innate immune system are known targets for enhancing vaccine efficacy. We investigated whether imiquimod, a synthetic TLR7 agonist, can expedite the immune response against influenza virus infection when combined with influenza vaccine. BALB/c mice were immunized intraperitoneally with monovalent A(H1N1)pdm09 vaccine combined with imiquimod (VCI) 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 the VCI group (60%, mean survival time[MST], 11 days) than in the vaccine-alone (30%; MST, 8.8 days), imiquimod-alone (5%; MST, 8.4 days), and phosphate-buffered saline (PBS) (0%; MST, 6.2 days) groups (P < 0.01). In the VCI group, 45 and 35% of the mice survived even when they were infected 2 days or 1 day after immunization. Virus-specific serum IgM, IgG, and neutralizing antibodies appeared earlier with higher geometric mean titers in the VCI group than in the control groups. The pulmonary viral load was significantly lower at all time points postinfection in the VCI, vaccine-alone, and imiquimod-alone groups than in 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 immune protection. Moreover, increased gamma interferon mRNA expression and IgG isotype switching, which are markers of the Th1 response induced by imiquimod, were not apparent in our mouse model. The mechanisms of imiquimod-induced immune protection deserve further study. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Persistent Identifierhttp://hdl.handle.net/10722/203113
ISSN
2015 Impact Factor: 2.277
2015 SCImago Journal Rankings: 1.329
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, AJX-
dc.contributor.authorLi, C-
dc.contributor.authorTo, KKW-
dc.contributor.authorZhu, HS-
dc.contributor.authorLee, ACY-
dc.contributor.authorLi, CG-
dc.contributor.authorChan, JFW-
dc.contributor.authorHung, IFN-
dc.contributor.authorYuen, KY-
dc.date.accessioned2014-09-19T11:31:45Z-
dc.date.available2014-09-19T11:31:45Z-
dc.date.issued2014-
dc.identifier.citationClinical and vaccine immunology, 2014, v. 21 n. 4, p. 570-579-
dc.identifier.issn1556-6811-
dc.identifier.urihttp://hdl.handle.net/10722/203113-
dc.description.abstractToll-like receptors (TLRs) of the innate immune system are known targets for enhancing vaccine efficacy. We investigated whether imiquimod, a synthetic TLR7 agonist, can expedite the immune response against influenza virus infection when combined with influenza vaccine. BALB/c mice were immunized intraperitoneally with monovalent A(H1N1)pdm09 vaccine combined with imiquimod (VCI) 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 the VCI group (60%, mean survival time[MST], 11 days) than in the vaccine-alone (30%; MST, 8.8 days), imiquimod-alone (5%; MST, 8.4 days), and phosphate-buffered saline (PBS) (0%; MST, 6.2 days) groups (P < 0.01). In the VCI group, 45 and 35% of the mice survived even when they were infected 2 days or 1 day after immunization. Virus-specific serum IgM, IgG, and neutralizing antibodies appeared earlier with higher geometric mean titers in the VCI group than in the control groups. The pulmonary viral load was significantly lower at all time points postinfection in the VCI, vaccine-alone, and imiquimod-alone groups than in 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 immune protection. Moreover, increased gamma interferon mRNA expression and IgG isotype switching, which are markers of the Th1 response induced by imiquimod, were not apparent in our mouse model. The mechanisms of imiquimod-induced immune protection deserve further study. Copyright © 2014, American Society for Microbiology. All Rights Reserved.-
dc.languageeng-
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://cdli.asm.org/-
dc.relation.ispartofClinical and vaccine immunology-
dc.rightsClinical and vaccine immunology. Copyright © American Society for Microbiology.-
dc.titleToll-like receptor 7 agonist imiquimod in combination with influenza vaccine expedites and augments humoral immune responses against influenza A(H1N1)pdm09 virus infection in BALB/c mice-
dc.typeArticle-
dc.identifier.emailZhang, AJX: zhangajx@hkucc.hku.hk-
dc.identifier.emailLi, C: canlee@hku.hk-
dc.identifier.emailTo, KKW: kelvinto@hkucc.hku.hk-
dc.identifier.emailZhu, HS: zhs007@hku.hk-
dc.identifier.emailLee, ACY: cyalee@hku.hk-
dc.identifier.emailLi, CG: max2012@hku.hk-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailHung, IFN: ivanhung@hkucc.hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.authorityZhang, AJX=rp00413-
dc.identifier.authorityTo, KKW=rp01384-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityHung, IFN=rp00508-
dc.identifier.authorityYuen, KY=rp00366-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1128/CVI.00816-13-
dc.identifier.pmid24521786-
dc.identifier.pmcidPMC3993121-
dc.identifier.scopuseid_2-s2.0-84897937018-
dc.identifier.hkuros238441-
dc.identifier.volume21-
dc.identifier.issue4-
dc.identifier.spage570-
dc.identifier.epage579-
dc.identifier.isiWOS:000333678500015-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats