Hydrogel-Delivered GM-CSF Overcomes Nonresponsiveness to Hepatitis B Vaccine through the Recruitment and Activation of Dendritic Cells

摘要: The standard hepatitis B surface Ag (HBsAg) vaccine fails to induce anti-hepatitis Abs in 5-10% of healthy subjects, a phenomenon known as HBsAg nonresponsiveness, which is closely related HLA class II alleles and impaired Th cell responses these subjects. We hypothesized that GM-CSF, potent adjuvant enhancing the Ag-presentation activity APCs, might help generate nonresponders, subsequently providing for cells produce Abs. used thermosensitive biodegradable copolymer (hydrogel) system codeliver GM-CSF achieve maximal local cytokine at injection site. In responder mouse strains, hydrogel-formulated plus (Gel/HBs+GM) elicited much greater Ab titers proliferative than commercial aluminum-formulated or free HBsAg. effect Gel/HBs+GM was dependent upon release GM-CSF. More importantly, high HBsAg-specific B10.M mice, strain does not respond current because its H-2 haplotype. Analysis draining lymph nodes vaccine-treated mice revealed an elevated number CD11c(+) dendritic showing enhanced expression MHC variety costimulatory molecules. These results demonstrate represent simple effective method next-generation virus vaccines inducing nonresponders.