title: PD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8+ T cells in mice.
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.
authors: AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors: Jingying
authors: J
authors: Zhou
authors: Allen K L
authors: AK
authors: Cheung
authors: Zhiwu
authors: Z
authors: Tan
authors: Haibo
authors: H
authors: Wang
authors: Wenbo
authors: W
authors: Yu
authors: Yanhua
authors: Y
authors: Du
authors: Yuanxi
authors: Y
authors: Kang
authors: Xiaofan
authors: X
authors: Lu
authors: Li
authors: L
authors: Liu
authors: Kwok-Yung
authors: KY
authors: Yuen
authors: Zhiwei
authors: Z
authors: Chen
mesh_terms: D016915:AIDS Vaccines; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D005260:Female; D057809:HEK293 Cells; D016655:HIV Core Protein p24 / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA
chemical_list: D016915:AIDS Vaccines; D000956:Antigens, Viral; D016655:HIV Core Protein p24; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D018664:Interleukin-12
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