title: Novel thermal-sensitive hydrogel enhances both humoral and cell-mediated immune responses by intranasal vaccine delivery.
abstract: A novel thermal sensitive hydrogel was formulated with N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC) and α, β-glycerophosphate (α, β-GP). A serial of hydrogels containing different amount of GP and HTCC with diverse quarternize degree (QD, 41%, 59%, 79.5%, and 99%) were prepared and characterized by rheological method. The hydrogel was subsequently evaluated for intranasal vaccine delivery with adenovirus based Zaire Ebola virus glycoprotein antigen (Ad-GPZ). Results showed that moderate quarternized HTCC (60% and 79.5%) hydrogel/antigen formulations induced highest IgG, IgG1, and IgG2a antibody titers in serum, as well as mucosal IgA responses in lung wash, which may attributed to the prolonged antigen residence time due to the thermal-sensitivity of this hydrogel. Furthermore, CD8(+) splenocytes for IFN-γ positive cell assay and the release profile of Th1/Th2 type cytokines (IFN-γ, IL-2, IL-10, and IL-4) showed that hydrogel/Ad-GPZ generated an overwhelmingly enhanced Th1 biased cellular immune response. In addition, this hydrogel displayed low toxicity to nasal tissue and epithelial cells even by frequently intranasal dosing of hydrogel. All these results strongly supported this hydrogel as a safe and effective delivery system for nasal immunization.
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, PR China.
authors.forename: Youbin
authors.initials: Y
authors.lastname: Wu
authors.forename: Shipo
authors.initials: S
authors.lastname: Wu
authors.forename: Lihua
authors.initials: L
authors.lastname: Hou
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Meng
authors.initials: M
authors.lastname: Zhou
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Su
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Guanghui
authors.initials: G
authors.lastname: Ma
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000281:Administration, Intranasal; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D046129:Ebola Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity; D005260:Female; D005994:Glycerophosphates; D020100:Hydrogels; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013696:Temperature; D018417:Th1 Cells / Q000276:immunology; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D046129:Ebola Vaccines; D005994:Glycerophosphates; D020100:Hydrogels; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C572320:N-((2-hydroxy-3-trimethylammonium)propyl)chitosan chloride; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus; D048271:Chitosan