title: Induction of long-term immunity against respiratory syncytial virus glycoprotein by an osmotic polymeric nanocarrier.
abstract: Respiratory syncytial virus (RSV) is one of the most common causes of viral deaths in infants worldwide, yet no effective vaccines are available. Here, we report an osmotically active polysaccharide-based polysorbitol transporter (PST) prepared from sorbitol diacrylate and low-molecular-weight polyethylenimine (PEI) showing a potent, yet safe, adjuvant activity and acting as an effective delivery tool for RSV glycoprotein (RGp) antigen. PST showed no toxicity in vitro or in vivo, unlike PEI and the well-known experimental mucosal adjuvant cholera toxin (CT). PST formed nano-sized complexes with RGp by simple mixing, without affecting antigenic stability. The complexes exhibited negative surface charges that made them highly efficient in the selective activation of phagocytic cells and enhancement of phagocytic uptake. This resulted in an improved cytokine production and in the significant augmentation of RGp-specific antibody production, which persisted for over 200 days. Interestingly, PST/RGp enhanced phagocytic uptake owing to the osmotic property of PST and its negative zeta potential, suggesting that PST could selectively stimulate phagocytic cells, thereby facilitating a long-lived antigen-specific immune response, which was presumably further enhanced by the polysaccharide properties of PST.
authors.affiliation: Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea; World Class University Biomodulation Major & Center for Food and Bioconvergence, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Jannatul
authors.initials: J
authors.lastname: Firdous
authors.affiliation: Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea; World Class University Biomodulation Major & Center for Food and Bioconvergence, Seoul National University, Seoul 151-742, Republic of Korea; Brigham and Women's Hospital & Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Mohammad Ariful
authors.initials: MA
authors.lastname: Islam
authors.affiliation: Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea; World Class University Biomodulation Major & Center for Food and Bioconvergence, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Sung-Moo
authors.initials: SM
authors.lastname: Park
authors.affiliation: Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea; Laboratory Science Division, International Vaccine Institute, Seoul 151-919, Republic of Korea.
authors.forename: In-Su
authors.initials: IS
authors.lastname: Cheon
authors.affiliation: Laboratory Science Division, International Vaccine Institute, Seoul 151-919, Republic of Korea.
authors.forename: Byoung-Shik
authors.initials: BS
authors.lastname: Shim
authors.affiliation: Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Hyo-Shin
authors.initials: HS
authors.lastname: Yoon
authors.affiliation: Laboratory Science Division, International Vaccine Institute, Seoul 151-919, Republic of Korea.
authors.forename: Manki
authors.initials: M
authors.lastname: Song
authors.affiliation: Division of Life and Pharmaceutical Sciences, Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Yun-Jaie
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Immunology & Laboratory of Dendritic Cell Differentiation & Regulation, School of Medicine, Konkuk University, Chungju 380-701, Republic of Korea.
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
authors.affiliation: Institute of Protein Biochemistry, Consiglio Nazionale delle Ricerche, Via P. Castellino111, 80131 Napoli, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Boraschi
authors.affiliation: Department of Oral Microbiology and Immunology & DRI, School of Dentistry, Seoul National University, Seoul 110-740, Republic of Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Han
authors.affiliation: Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea. Electronic address: chocs@snu.ac.kr.
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
authors.affiliation: Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea; World Class University Biomodulation Major & Center for Food and Bioconvergence, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: cyun@snu.ac.kr.
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
mesh_terms: D000818:Animals; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000648:ultrastructure; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009994:Osmolar Concentration; D010587:Phagocytosis / Q000187:drug effects; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D012136:Respiratory Syncytial Viruses / Q000187:drug effects / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D006023:Glycoproteins; D011091:Polyesters; D014764:Viral Proteins; C569756:polysorbitol-based osmotically active transporter polymer; D011094:Polyethyleneimine; D016650:Fluorescein-5-isothiocyanate
keywords: Adjuvant activity; Enhanced phagocytosis; Long-term antibody response; Osmotically active polysorbitol transporter; RSV glycoprotein