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Article: PD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8+ T cells in mice

TitlePD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8+ T cells in mice
Authors
Issue Date2013
PublisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org
Citation
Journal of Clinical Investigation, 2013, v. 123 n. 6, p. 2629-2642 How to Cite?
AbstractViral vector-based vaccines that induce protective CD8+ T cell immunity can prevent or control pathogenic SIV infections, but issues of preexisting immunity and safety have impeded their implementation in HIV-1. Here, we report the development of what we believe to be a novel antigen-targeting DNA vaccine strategy that exploits the binding of programmed death-1 (PD1) to its ligands expressed on dendritic cells (DCs) by fusing soluble PD1 with HIV-1 GAG p24 antigen. As compared with non-DC-targeting vaccines, intramuscular immunization via electroporation (EP) of the fusion DNA in mice elicited consistently high frequencies of GAG-specific, broadly reactive, polyfunctional, long-lived, and cytotoxic CD8+ T cells and robust anti-GAG antibody titers. Vaccination conferred remarkable protection against mucosal challenge with vaccinia GAG viruses. Soluble PD1-based vaccination potentiated CD8+ T cell responses by enhancing antigen binding and uptake in DCs and activation in the draining lymph node. It also increased IL-12-producing DCs and engaged antigen cross-presentation when compared with anti-DEC205 antibody-mediated DC targeting. The high frequency of durable and protective GAG-specific CD8+ T cell immunity induced by soluble PD1-based vaccination suggests that PD1-based DNA vaccines could potentially be used against HIV-1 and other pathogens.
Persistent Identifierhttp://hdl.handle.net/10722/186077
ISSN
2015 Impact Factor: 12.575
2015 SCImago Journal Rankings: 8.764
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhou, Jen_US
dc.contributor.authorCheung, KLAen_US
dc.contributor.authorTan, Zen_US
dc.contributor.authorWang, Hen_US
dc.contributor.authorYu, Wen_US
dc.contributor.authorDu, Yen_US
dc.contributor.authorKang, Yen_US
dc.contributor.authorLu, Xen_US
dc.contributor.authorLiu, Len_US
dc.contributor.authorYuen, KYen_US
dc.contributor.authorChen, Z-
dc.date.accessioned2013-08-20T11:53:30Z-
dc.date.available2013-08-20T11:53:30Z-
dc.date.issued2013en_US
dc.identifier.citationJournal of Clinical Investigation, 2013, v. 123 n. 6, p. 2629-2642en_US
dc.identifier.issn0021-9738-
dc.identifier.urihttp://hdl.handle.net/10722/186077-
dc.description.abstractViral vector-based vaccines that induce protective CD8+ T cell immunity can prevent or control pathogenic SIV infections, but issues of preexisting immunity and safety have impeded their implementation in HIV-1. Here, we report the development of what we believe to be a novel antigen-targeting DNA vaccine strategy that exploits the binding of programmed death-1 (PD1) to its ligands expressed on dendritic cells (DCs) by fusing soluble PD1 with HIV-1 GAG p24 antigen. As compared with non-DC-targeting vaccines, intramuscular immunization via electroporation (EP) of the fusion DNA in mice elicited consistently high frequencies of GAG-specific, broadly reactive, polyfunctional, long-lived, and cytotoxic CD8+ T cells and robust anti-GAG antibody titers. Vaccination conferred remarkable protection against mucosal challenge with vaccinia GAG viruses. Soluble PD1-based vaccination potentiated CD8+ T cell responses by enhancing antigen binding and uptake in DCs and activation in the draining lymph node. It also increased IL-12-producing DCs and engaged antigen cross-presentation when compared with anti-DEC205 antibody-mediated DC targeting. The high frequency of durable and protective GAG-specific CD8+ T cell immunity induced by soluble PD1-based vaccination suggests that PD1-based DNA vaccines could potentially be used against HIV-1 and other pathogens.-
dc.languageengen_US
dc.publisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org-
dc.relation.ispartofJournal of Clinical Investigationen_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshCD8-Positive T-Lymphocytes - immunology - virology-
dc.subject.meshHIV Core Protein p24 - immunology-
dc.subject.meshHIV Infections - prevention and control-
dc.subject.meshHIV-1 - immunology-
dc.subject.meshProgrammed Cell Death 1 Receptor - immunology-
dc.titlePD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8+ T cells in miceen_US
dc.typeArticleen_US
dc.identifier.emailCheung, KLA: allenc@hku.hken_US
dc.identifier.emailWang, H: hbwang@hkucc.hku.hken_US
dc.identifier.emailDu, Y: biodu@hku.hken_US
dc.identifier.emailLiu, L: liuli71@hkucc.hku.hken_US
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hken_US
dc.identifier.emailChen, Z: zchenai@hkucc.hku.hk-
dc.identifier.authorityLiu, L=rp00268en_US
dc.identifier.authorityYuen, KY=rp00366en_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1172/JCI64704-
dc.identifier.pmid23635778-
dc.identifier.pmcidPMC3668817-
dc.identifier.scopuseid_2-s2.0-84878552360-
dc.identifier.hkuros219240en_US
dc.identifier.volume123en_US
dc.identifier.issue6-
dc.identifier.spage2629en_US
dc.identifier.epage2642en_US
dc.identifier.isiWOS:000320093100032-
dc.publisher.placeUnited States-

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