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Conference Paper: A novel programmed death 1 isoform-based fusion DNA vaccine enhances functional antigen-specific CD8+ T cell immunity
Title | A novel programmed death 1 isoform-based fusion DNA vaccine enhances functional antigen-specific CD8+ T cell immunity |
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Authors | |
Issue Date | 2013 |
Publisher | American Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org |
Citation | The American Association of Immunologists (AAI) 2013 Annual Meeting on Immunology (Immunology 2013), Honolulu, HI., 3-7 May 2013. In Journal of Immunology, 2013, v. 190 meeting abstract suppl., abstract no. 179.12 How to Cite? |
Abstract | Inducing an effective CD8+ T cell immunity is important in the protection and elimination of infectious pathogens. Programmed death-1 (PD1) up-regulation in in chronic infections (e.g. HIV-1 and TB) results in 'exhausted' function of CD8+ T cells, but is restored by blockade of the PD1/PD-L pathway with antibodies or a soluble form of (s)PD1. Apart from sPD1, the other three spliced variants previously identified currently have no known function. In this study, we identified a new isoform of human PD1 that contains a 42-nucleotide in-frame deletion located at exon 2 near its IgV domain found expressed in PBMCs, named {Delta}42PD1. We found that {Delta}42PD1 is distinct from PD1 as it does not engage PD-L1 or PD-L2 and capable of inducing the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). Next, we used {Delta}42PD1 as an intramolecular adjuvant to construct a DNA fusion vaccine with HIV-1 Gag p24 antigen. Following immunization in Balb/c mice, a significantly enhanced level of anti-p24 antibody titer and p24-specific CD8+ T cell responses were elicited that persisted for at least 7.5 months. Furthermore, vaccinated mice were protected against pathogenic vaccinia-Gag virus challenge, likely due to the improved proliferative and cytotoxic functions of the elicited CD8+ T cells. Therefore, our study demonstrates that a novel {Delta}42PD1 variant that amplifies the generation of antigen-specific CD8+ T cell immunity when used in a DNA vaccine. |
Description | Session: Immunotherapy and Vaccines: Infectious Diseases 1 |
Persistent Identifier | http://hdl.handle.net/10722/186865 |
ISSN | 2023 Impact Factor: 3.6 2023 SCImago Journal Rankings: 1.558 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Cheung, KLA | en_US |
dc.contributor.author | Zhou, J | en_US |
dc.contributor.author | Liu, H | en_US |
dc.contributor.author | Tan, Z | en_US |
dc.contributor.author | Chen, Z | en_US |
dc.date.accessioned | 2013-08-20T12:22:29Z | - |
dc.date.available | 2013-08-20T12:22:29Z | - |
dc.date.issued | 2013 | en_US |
dc.identifier.citation | The American Association of Immunologists (AAI) 2013 Annual Meeting on Immunology (Immunology 2013), Honolulu, HI., 3-7 May 2013. In Journal of Immunology, 2013, v. 190 meeting abstract suppl., abstract no. 179.12 | en_US |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.uri | http://hdl.handle.net/10722/186865 | - |
dc.description | Session: Immunotherapy and Vaccines: Infectious Diseases 1 | - |
dc.description.abstract | Inducing an effective CD8+ T cell immunity is important in the protection and elimination of infectious pathogens. Programmed death-1 (PD1) up-regulation in in chronic infections (e.g. HIV-1 and TB) results in 'exhausted' function of CD8+ T cells, but is restored by blockade of the PD1/PD-L pathway with antibodies or a soluble form of (s)PD1. Apart from sPD1, the other three spliced variants previously identified currently have no known function. In this study, we identified a new isoform of human PD1 that contains a 42-nucleotide in-frame deletion located at exon 2 near its IgV domain found expressed in PBMCs, named {Delta}42PD1. We found that {Delta}42PD1 is distinct from PD1 as it does not engage PD-L1 or PD-L2 and capable of inducing the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). Next, we used {Delta}42PD1 as an intramolecular adjuvant to construct a DNA fusion vaccine with HIV-1 Gag p24 antigen. Following immunization in Balb/c mice, a significantly enhanced level of anti-p24 antibody titer and p24-specific CD8+ T cell responses were elicited that persisted for at least 7.5 months. Furthermore, vaccinated mice were protected against pathogenic vaccinia-Gag virus challenge, likely due to the improved proliferative and cytotoxic functions of the elicited CD8+ T cells. Therefore, our study demonstrates that a novel {Delta}42PD1 variant that amplifies the generation of antigen-specific CD8+ T cell immunity when used in a DNA vaccine. | - |
dc.language | eng | en_US |
dc.publisher | American Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org | - |
dc.relation.ispartof | Journal of Immunology | en_US |
dc.title | A novel programmed death 1 isoform-based fusion DNA vaccine enhances functional antigen-specific CD8+ T cell immunity | en_US |
dc.type | Conference_Paper | en_US |
dc.identifier.email | Cheung, KLA: allenc@hku.hk | en_US |
dc.identifier.email | Liu, H: liuhg@hkucc.hku.hk | en_US |
dc.identifier.email | Chen, Z: zchenai@hku.hk | en_US |
dc.identifier.authority | Chen, Z=rp00243 | en_US |
dc.identifier.hkuros | 219250 | en_US |
dc.identifier.volume | 190 | - |
dc.identifier.issue | meeting abstract suppl. | - |
dc.identifier.isi | WOS:000322987106061 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 0022-1767 | - |