title: Cyclophilin A as a potential genetic adjuvant to improve HIV-1 Gag DNA vaccine immunogenicity by eliciting broad and long-term Gag-specific cellular immunity in mice.
abstract: Previous research has shown that host Cyclophilin A (CyPA) can promote dendritic cell maturation and the subsequent innate immune response when incorporated into an HIV-1 Gag protein to circumvent the resistance of dendritic cells to HIV-1 infection. This led us to hypothesize that CyPA may improve HIV-1 Gag-specific vaccine immunogenicity via binding with Gag antigen. The adjuvant effect of CyPA was evaluated using a DNA vaccine with single or dual expression cassettes. Mouse studies indicated that CyPA specifically and markedly promoted HIV-1 Gag-specific cellular immunity but not an HIV-1 Env-specific cellular response. The Gag/CyPA dual expression cassettes stimulated a greater Gag-specific cellular immune response, than Gag immunization alone. Furthermore, CyPA induced a broad Gag-specific T cell response and strong cellular immunity that lasted up to 5 months. In addition, CyPA skewed to cellular rather than humoral immunity. To investigate the mechanisms of the adjuvant effect, site-directed mutagenesis in CyPA, including active site residues H54Q and F60A resulted in mutants that were co-expressed with Gag in dual cassettes. The immune response to this vaccine was analyzed in vivo. Interestingly, the wild type CyPA markedly increased Gag cellular immunity, but the H54Q and F60A mutants drastically reduced CyPA adjuvant activation. Therefore, we suggest that the adjuvant effect of CyPA was based on Gag-CyPA-specific interactions. Herein, we report that Cyclophilin A can augment HIV-1 Gag-specific cellular immunity as a genetic adjuvant in multiplex DNA immunization strategies, and that activity of this adjuvant is specific, broad, long-term, and based on Gag-CyPA interaction.
authors: a State Key Laboratory for Infectious Disease Prevention and Control; National Center for AIDS/STD Control and Prevention; Chinese Center for Disease Control and Prevention ; Beijing , China.
authors: Jue
authors: J
authors: Hou
authors: a State Key Laboratory for Infectious Disease Prevention and Control; National Center for AIDS/STD Control and Prevention; Chinese Center for Disease Control and Prevention ; Beijing , China.
authors: Qicheng
authors: Q
authors: Zhang
authors: a State Key Laboratory for Infectious Disease Prevention and Control; National Center for AIDS/STD Control and Prevention; Chinese Center for Disease Control and Prevention ; Beijing , China.
authors: Zheng
authors: Z
authors: Liu
authors: a State Key Laboratory for Infectious Disease Prevention and Control; National Center for AIDS/STD Control and Prevention; Chinese Center for Disease Control and Prevention ; Beijing , China.
authors: Shuhui
authors: S
authors: Wang
authors: a State Key Laboratory for Infectious Disease Prevention and Control; National Center for AIDS/STD Control and Prevention; Chinese Center for Disease Control and Prevention ; Beijing , China.
authors: Dan
authors: D
authors: Li
authors: a State Key Laboratory for Infectious Disease Prevention and Control; National Center for AIDS/STD Control and Prevention; Chinese Center for Disease Control and Prevention ; Beijing , China.
authors: Chang
authors: C
authors: Liu
authors: a State Key Laboratory for Infectious Disease Prevention and Control; National Center for AIDS/STD Control and Prevention; Chinese Center for Disease Control and Prevention ; Beijing , China.
authors: Ying
authors: Y
authors: Liu
authors: a State Key Laboratory for Infectious Disease Prevention and Control; National Center for AIDS/STD Control and Prevention; Chinese Center for Disease Control and Prevention ; Beijing , China.
authors: Yiming
authors: Y
authors: Shao
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D021984:Cyclophilin A / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D019444:Vaccines, DNA; D054301:gag Gene Products, Human Immunodeficiency Virus; D021984:Cyclophilin A
keywords: HIV-1 Gag; cyclophilin A; genetic adjuvant; immunogenicity; protein interaction