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Article: Potentiating Functional Antigen-specific CD8+ T Cell Immunity by a Novel PD1 Isoform-based Fusion DNA Vaccine

TitlePotentiating Functional Antigen-specific CD8+ T Cell Immunity by a Novel PD1 Isoform-based Fusion DNA Vaccine
Authors
Issue Date2013
PublisherCell Press. The Journal's web site is located at https://www.cell.com/molecular-therapy-family/home
Citation
Molecular Therapy, 2013, v. 21 n. 7, p. 1445-1455 How to Cite?
AbstractUnderstanding and identifying new ways of mounting an effective CD8+ T cell immune response is important for eliminating infectious pathogens. Although upregulated programmed death-1 (PD1) in chronic infections (such as HIV-1 and tuberculosis) impedes T cell responses, blocking this PD1/PD-L pathway could functionally rescue the “exhausted” T cells. However, there exists a number of PD1 spliced variants with unknown biological function. Here, we identified a new isoform of human PD1 (Δ42PD1) that contains a 42-nucleotide in-frame deletion located at exon 2 domain found expressed in peripheral blood mononuclear cells (PBMCs). Δ42PD1 appears to function distinctly from PD1, as it does not engage PD-L1/PD-L2 but its recombinant form could induce proinflammatory cytokines. We utilized Δ42PD1 as an intramolecular adjuvant to develop a fusion DNA vaccine with HIV-1 Gag p24 antigen to immunize mice, which elicited a significantly enhanced level of anti-p24 IgG1/IgG2a antibody titers, and important p24-specific and tetramer+CD8+ T cells responses that lasted for ≥7.5 months. Furthermore, p24-specific CD8+ T cells remain functionally improved in proliferative and cytolytic capacities. Importantly, the enhanced antigen-specific immunity protected mice against pathogenic viral challenge and tumor growth. Thus, this newly identified PD1 variant (Δ42PD1) amplifies the generation of antigen-specific CD8+ T cell immunity when used in a DNA vaccine.
Persistent Identifierhttp://hdl.handle.net/10722/186076
ISSN
2023 Impact Factor: 12.1
2023 SCImago Journal Rankings: 3.736
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhou, J-
dc.contributor.authorCheung, AKL-
dc.contributor.authorLiu, H-
dc.contributor.authorTan, Z-
dc.contributor.authorTang, X-
dc.contributor.authorKang, Y-
dc.contributor.authorDu, Y-
dc.contributor.authorWang, H-
dc.contributor.authorLiu, L-
dc.contributor.authorChen, Z-
dc.date.accessioned2013-08-20T11:53:30Z-
dc.date.available2013-08-20T11:53:30Z-
dc.date.issued2013-
dc.identifier.citationMolecular Therapy, 2013, v. 21 n. 7, p. 1445-1455-
dc.identifier.issn1525-0016-
dc.identifier.urihttp://hdl.handle.net/10722/186076-
dc.description.abstractUnderstanding and identifying new ways of mounting an effective CD8+ T cell immune response is important for eliminating infectious pathogens. Although upregulated programmed death-1 (PD1) in chronic infections (such as HIV-1 and tuberculosis) impedes T cell responses, blocking this PD1/PD-L pathway could functionally rescue the “exhausted” T cells. However, there exists a number of PD1 spliced variants with unknown biological function. Here, we identified a new isoform of human PD1 (Δ42PD1) that contains a 42-nucleotide in-frame deletion located at exon 2 domain found expressed in peripheral blood mononuclear cells (PBMCs). Δ42PD1 appears to function distinctly from PD1, as it does not engage PD-L1/PD-L2 but its recombinant form could induce proinflammatory cytokines. We utilized Δ42PD1 as an intramolecular adjuvant to develop a fusion DNA vaccine with HIV-1 Gag p24 antigen to immunize mice, which elicited a significantly enhanced level of anti-p24 IgG1/IgG2a antibody titers, and important p24-specific and tetramer+CD8+ T cells responses that lasted for ≥7.5 months. Furthermore, p24-specific CD8+ T cells remain functionally improved in proliferative and cytolytic capacities. Importantly, the enhanced antigen-specific immunity protected mice against pathogenic viral challenge and tumor growth. Thus, this newly identified PD1 variant (Δ42PD1) amplifies the generation of antigen-specific CD8+ T cell immunity when used in a DNA vaccine.-
dc.languageeng-
dc.publisherCell Press. The Journal's web site is located at https://www.cell.com/molecular-therapy-family/home-
dc.relation.ispartofMolecular Therapy-
dc.titlePotentiating Functional Antigen-specific CD8+ T Cell Immunity by a Novel PD1 Isoform-based Fusion DNA Vaccine-
dc.typeArticle-
dc.identifier.emailCheung, AKL: allenc@hku.hk-
dc.identifier.emailLiu, H: liuhg@hkucc.hku.hk-
dc.identifier.emailTan, Z: zwtan@hku.hk-
dc.identifier.emailDu, Y: biodu@hku.hk-
dc.identifier.emailWang, H: hbwang@hkucc.hku.hk-
dc.identifier.emailLiu, L: liuli71@hkucc.hku.hk-
dc.identifier.emailChen, Z: zchenai@hku.hk-
dc.identifier.authorityTan, Z=rp02817-
dc.identifier.authorityLiu, L=rp00268-
dc.identifier.authorityChen, Z=rp00243-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1038/mt.2013.63-
dc.identifier.pmid23587922-
dc.identifier.pmcidPMC3702111-
dc.identifier.scopuseid_2-s2.0-84879694758-
dc.identifier.hkuros219230-
dc.identifier.volume21-
dc.identifier.issue7-
dc.identifier.spage1445-
dc.identifier.epage1455-
dc.identifier.isiWOS:000321112500018-
dc.publisher.placeUnited States-

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