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Conference Paper: A novel programmed death 1 isoform-based fusion DNA vaccine enhances functional antigen-specific CD8+ T cell immunity

TitleA novel programmed death 1 isoform-based fusion DNA vaccine enhances functional antigen-specific CD8+ T cell immunity
Authors
Issue Date2013
PublisherAmerican 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?
AbstractInducing 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.
DescriptionSession: Immunotherapy and Vaccines: Infectious Diseases 1
Persistent Identifierhttp://hdl.handle.net/10722/186865
ISSN
2015 Impact Factor: 4.985
2015 SCImago Journal Rankings: 3.549

 

DC FieldValueLanguage
dc.contributor.authorCheung, KLAen_US
dc.contributor.authorZhou, Jen_US
dc.contributor.authorLiu, Hen_US
dc.contributor.authorTan, Zen_US
dc.contributor.authorChen, Zen_US
dc.date.accessioned2013-08-20T12:22:29Z-
dc.date.available2013-08-20T12:22:29Z-
dc.date.issued2013en_US
dc.identifier.citationThe 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. 179.12en_US
dc.identifier.issn0022-1767-
dc.identifier.urihttp://hdl.handle.net/10722/186865-
dc.descriptionSession: Immunotherapy and Vaccines: Infectious Diseases 1-
dc.description.abstractInducing 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.languageengen_US
dc.publisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org-
dc.relation.ispartofJournal of Immunologyen_US
dc.titleA novel programmed death 1 isoform-based fusion DNA vaccine enhances functional antigen-specific CD8+ T cell immunityen_US
dc.typeConference_Paperen_US
dc.identifier.emailCheung, KLA: allenc@hku.hken_US
dc.identifier.emailLiu, H: liuhg@hkucc.hku.hken_US
dc.identifier.emailChen, Z: zchenai@hku.hken_US
dc.identifier.authorityChen, Z=rp00243en_US
dc.identifier.hkuros219250en_US
dc.identifier.volume190-
dc.identifier.issuemeeting abstract suppl.-
dc.publisher.placeUnited States-

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