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Dendritic Cell Mediated Delivery of Plasmid DNA Encoding LAMP/HIV-1 Gag Fusion Immunogen Enhances T Cell Epitope Responses in HLA DR4 Transgenic Mice

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dc.contributor.authorSimon, Gregory G.
dc.contributor.authorHu, Yongli
dc.contributor.authorKHAN, MOHAMMAD ASİF
dc.contributor.authorZhou, Jingshi
dc.contributor.authorSalmon, Jerome
dc.contributor.authorChikhlikar, Priya R.
dc.contributor.authorJung, Keun-Ok
dc.contributor.authorMarques, Ernesto T. A.
dc.contributor.authorAugust, J. Thomas
dc.contributor.institutionauthorKHAN, MOHAMMAD ASİF
dc.date.accessioned2021-09-01T20:59:16Z
dc.date.available2021-09-01T20:59:16Z
dc.date.issued2010-01-01T00:00:00Z
dc.description.abstractThis 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 1x10(5) 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 pLAMP/gag DNA plasmid. Primary immunization with pLAMP/gag-transfected dendritic cells elicited the greatest number of peptide specific T-cell responses, as measured by ex vivo IFN-gamma ELISpot assay, both in BALB/c and HLA-DR4 transgenic mice. The pLAMP/gag-transfected dendritic cells prime and naked DNA boost immunization protocol also resulted in an increased apparent avidity of peptide in the ELISpot assay. Strikingly, 20 of 25 peptide-specific T-cell responses in the HLA-DR4 transgenic mice contained sequences that corresponded, entirely or partially to 18 of the 19 human HLA-DR4 epitopes listed in the HIV molecular immunology database. Selection of the most conserved epitope peptides as vaccine targets was facilitated by analysis of their representation and variability in all reported sequences. These data provide a model system that demonstrates a) the superiority of immunization with dendritic cells transfected with LAMP/gag plasmid DNA, as compared to naked DNA, b) the value of HLA transgenic mice as a model system for the identification and evaluation of epitope-based vaccine strategies, and c) the application of variability analysis across reported sequences in public databases for selection of historically conserved HIV epitopes as vaccine targets.
dc.identifier.citationSimon G. G. , Hu Y., KHAN M. A. , Zhou J., Salmon J., Chikhlikar P. R. , Jung K., Marques E. T. A. , August J. T. , -Dendritic Cell Mediated Delivery of Plasmid DNA Encoding LAMP/HIV-1 Gag Fusion Immunogen Enhances T Cell Epitope Responses in HLA DR4 Transgenic Mice-, PLOS ONE, cilt.5, sa.1, 2010
dc.identifier.doi10.1371/journal.pone.0008574
dc.identifier.scopus77649099536
dc.identifier.urihttp://hdl.handle.net/20.500.12645/29335
dc.identifier.wosWOS:000273338500017
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleDendritic Cell Mediated Delivery of Plasmid DNA Encoding LAMP/HIV-1 Gag Fusion Immunogen Enhances T Cell Epitope Responses in HLA DR4 Transgenic Mice
dc.typeArticle
dspace.entity.typePublication
local.avesis.id22d60cab-2bac-4e07-9c63-c00d1403e339
local.publication.goal03 - Sağlık ve Kaliteli Yaşam
local.publication.isinternational1
relation.isAuthorOfPublication60fee672-8864-4711-ae92-5b9dd3bb0ef7
relation.isAuthorOfPublication.latestForDiscovery60fee672-8864-4711-ae92-5b9dd3bb0ef7
relation.isGoalOfPublication9c198c48-b603-4e2f-8366-04edcfc1224c
relation.isGoalOfPublication.latestForDiscovery9c198c48-b603-4e2f-8366-04edcfc1224c
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