Potentiating functional antigen-specific CD8+ T cell immunity by a novel PD1 isoform-based fusion DNA vaccine

Jingying Zhou, Allen KL Cheung, Henggui Liu, Zhiwu Tan, Xian Tang, Yuanxi Kang, Yanhua Du, Haibo Wang, Li Liu, Zhiwei Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

18 Citations (Scopus)

Abstract

Understanding 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.

Original languageEnglish
Pages (from-to)1445-1455
Number of pages11
JournalMolecular Therapy
Volume21
Issue number7
DOIs
Publication statusPublished - Jul 2013

Scopus Subject Areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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