Long-Term Programming of Antigen-Specific Immunity from Gene Expression Signatures in the PBMC of Rhesus Macaques Immunized with an SIV DNA Vaccine

摘要: While HIV-1-specific cellular immunity is thought to be critical for the suppression of viral replication, correlates protection have not yet been determined. Rhesus macaques (RM) are an important animal model study and development vaccines against HIV/AIDS. Our laboratory has helped develop DNA-based in which recent technological advances, including genetic optimization vivo electroporation (EP), dramatically boost their immunogenicity. In this study, RMs were immunized with a DNA vaccine individual plasmids encoding SIV gag, env, pol alone, or combination molecular adjuvant, plasmid expressing chemokine ligand 5 (RANTES), followed by EP. Along standard immunological assays, flow-based activation analysis without ex restimulation high-throughput gene expression was performed. Strong induced vaccination supported all assays PBMC microarray that identified up-regulation 563 sequences those involved interferon signaling. Furthermore, 699 differentially regulated these groups at peak viremia following SIVmac251 challenge. We observed RANTES-adjuvanted animals significantly better suppressing replication during chronic infection exhibited distinct pattern included immune cell-trafficking cell cycle genes. greater percentage vaccine-induced central memory CD8+ T-cells capable activated phenotype detected as measured analysis. Thus, co-immunization RANTES adjuvant EP led generation transcriptionally had protective efficacy than its alone counterpart. data may provide insight into mechanisms control using assays.