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- Publisher Website: 10.1172/JCI64704
- Scopus: eid_2-s2.0-84878552360
- PMID: 23635778
- WOS: WOS:000320093100032
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Article: PD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8+ T cells in mice
Title | PD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8+ T cells in mice |
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Authors | |
Issue Date | 2013 |
Publisher | American 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? |
Abstract | Viral 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 Identifier | http://hdl.handle.net/10722/186077 |
ISSN | 2023 Impact Factor: 13.3 2023 SCImago Journal Rankings: 4.833 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Zhou, J | en_US |
dc.contributor.author | Cheung, KLA | en_US |
dc.contributor.author | Tan, Z | en_US |
dc.contributor.author | Wang, H | en_US |
dc.contributor.author | Yu, W | en_US |
dc.contributor.author | Du, Y | en_US |
dc.contributor.author | Kang, Y | en_US |
dc.contributor.author | Lu, X | en_US |
dc.contributor.author | Liu, L | en_US |
dc.contributor.author | Yuen, KY | en_US |
dc.contributor.author | Chen, Z | - |
dc.date.accessioned | 2013-08-20T11:53:30Z | - |
dc.date.available | 2013-08-20T11:53:30Z | - |
dc.date.issued | 2013 | en_US |
dc.identifier.citation | Journal of Clinical Investigation, 2013, v. 123 n. 6, p. 2629-2642 | en_US |
dc.identifier.issn | 0021-9738 | - |
dc.identifier.uri | http://hdl.handle.net/10722/186077 | - |
dc.description.abstract | Viral 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.language | eng | en_US |
dc.publisher | American Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org | - |
dc.relation.ispartof | Journal of Clinical Investigation | en_US |
dc.rights | © 2013 The American Society for Clinical Investigation. | - |
dc.subject.mesh | CD8-Positive T-Lymphocytes - immunology - virology | - |
dc.subject.mesh | HIV Core Protein p24 - immunology | - |
dc.subject.mesh | HIV Infections - prevention and control | - |
dc.subject.mesh | HIV-1 - immunology | - |
dc.subject.mesh | Programmed Cell Death 1 Receptor - immunology | - |
dc.title | PD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8+ T cells in mice | en_US |
dc.type | Article | en_US |
dc.identifier.email | Cheung, KLA: allenc@hku.hk | en_US |
dc.identifier.email | Wang, H: hbwang@hkucc.hku.hk | en_US |
dc.identifier.email | Du, Y: biodu@hku.hk | en_US |
dc.identifier.email | Liu, L: liuli71@hkucc.hku.hk | en_US |
dc.identifier.email | Yuen, KY: kyyuen@hkucc.hku.hk | en_US |
dc.identifier.email | Chen, Z: zchenai@hkucc.hku.hk | - |
dc.identifier.authority | Liu, L=rp00268 | en_US |
dc.identifier.authority | Yuen, KY=rp00366 | en_US |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1172/JCI64704 | - |
dc.identifier.pmid | 23635778 | - |
dc.identifier.pmcid | PMC3668817 | - |
dc.identifier.scopus | eid_2-s2.0-84878552360 | - |
dc.identifier.hkuros | 219240 | en_US |
dc.identifier.volume | 123 | en_US |
dc.identifier.issue | 6 | - |
dc.identifier.spage | 2629 | en_US |
dc.identifier.epage | 2642 | en_US |
dc.identifier.isi | WOS:000320093100032 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 0021-9738 | - |