dendritic cell mediated delivery of plasmid dna encoding lamphiv-1 gag fusion immunogen enhances t cell epitope responses in hla dr4 transgenic mice树突细胞介导的质粒dna编码lamphiv-1 gag融合免疫原增强t细胞抗原决定基反应hla dr4转基因小鼠.pdfVIP

Dendritic Cell Mediated Delivery of Plasmid DNA Encoding LAMP/HIV-1 Gag Fusion Immunogen Enhances T Cell Epitope Responses in HLA DR4 Transgenic Mice 1 2 2 1 1 1 Gregory G. Simon *, Yongli Hu , Asif M. Khan , Jingshi Zhou , Jerome Salmon , Priya R. Chikhlikar , Keun-Ok Jung1, Ernesto T. A. Marques1,3, J. Thomas August1,3 1 Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, 2 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, 3 Department of Medicine, Division of Infectious Diseases, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America Abstract This report describes the identification and bioinformatics analysis of HLA-DR4-restricted HIV-1 Gag epitope peptides, and the application of dendritic cell mediated immunization of DNA plasmid constructs. BALB/c (H-2d) and HLA-DR4 (DRA1*0101, DRB1*0401) transgenic mice were immunized with immature dendritic cells transfected by a recombinant DNA plasmid encoding the lysosome-associated membrane protein-1/HIV-1 Gag (pLAMP/gag) chimera antigen. Three immunization protocols were compared: 1) primary subcutaneous immunization with 1 6105 immature dendritic cells transfected by electroporation with the pLAMP/gag DNA plasmid, and a second subcutaneous immunization with the naked pLAMP/gag DNA plasmid; 2) primary immunization as above, and a second subcutaneous immunization with a pool of overlapping peptides spanning the HIV-1 Gag sequence; and 3) immunization twice by subcutaneous injection of the