title: Maltosylated polyethylenimine-based triple nanocomplexes of human papillomavirus 16L1 protein and DNA as a vaccine co-delivery system.
abstract: To improve vaccine delivery, we herein designed a co-delivery system using a protein antigen and its encoding plasmid linked in nanocomplexes via maltosylated PEI (mPEI). Cationic mPEI was electrostatically complexed to a plasmid encoding the human papillomavirus (HPV) type 16L1 protein (pHPV16L1), and further complexed to a maltose binding protein (MBP)-fused human papillomavirus type 16L1 fusion protein (HPV16L1-MBP). The HPV16L1-MBP/mPEI/pHPV16L1 complexes were characterized by gel-retardation properties, zeta potentials and sizes. The intracellular co-delivery of protein and plasmid DNA vaccines was significantly higher for mPEI-based triple nanocomplexes than for a simple physical mixture of the proteins and DNA. Moreover, the cellular delivery of plasmid DNA using mPEI-based triple nanocomplexes resulted in higher expression levels comparable to those obtained using dual complexes of mPEI and the plasmid DNA. In vivo, co-immunization of mice with HPV16L1-MBP/mPEI/pHPV16L1 nanocomplexes triggered the highest levels of humoral immune responses among various vaccination groups. Moreover, the mPEI-based nanocomplexes significantly enhanced the number of interferon-γ producing CD8(+) T cells compared with the use of mixed proteins and plasmid DNA. These results suggest that the effective cellular co-delivery of MBP-fused antigen proteins and plasmid DNA using maltosylated PEI-based triple nanocomplexes could enhance the immunogenicity of HPV16L1 vaccines.
authors: College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors: Hee-Jeong
authors: HJ
authors: Cho
authors: Su-Eun
authors: SE
authors: Han
authors: Saewon
authors: S
authors: Im
authors: Young
authors: Y
authors: Lee
authors: Young Bong
authors: YB
authors: Kim
authors: Taehoon
authors: T
authors: Chun
authors: Yu-Kyoung
authors: YK
authors: Oh
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D058619:Maltose-Binding Proteins / Q000235:genetics / Q000276:immunology*; D008422:Materials Testing; D051379:Mice; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D010316:Particle Size; D011094:Polyethyleneimine / Q000737:chemistry* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology
chemical_list: D036022:Capsid Proteins; D058619:Maltose-Binding Proteins; D009856:Oncogene Proteins, Viral; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; C063317:L1 protein, Human papillomavirus type 16; D011094:Polyethyleneimine; D004247:DNA