title: Conjugating influenza a (H1N1) antigen to n-trimethylaminoethylmethacrylate chitosan nanoparticles improves the immunogenicity of the antigen after nasal administration.
abstract: As one of the most serious infectious respiratory diseases, influenza A (H1N1) is a great threat to human health, and it has created an urgent demand for effective vaccines. Nasal immunization can induce both systemic and mucosal immune responses against viruses, and it can serve as an ideal route for vaccination. However, the low immunogenicity of antigens on nasal mucosa is a high barrier for the development of nasal vaccines. In this study, we covalently conjugated an influenza A (H1N1) antigen to the surface of N-trimethylaminoethylmethacrylate chitosan (TMC) nanoparticles (H1N1-TMC/NP) through thioester bonds to increase the immunogenicity of the antigen after nasal administration. SDS-PAGE revealed that most of the antigen was conjugated on TMC nanoparticles, and an in vitro biological activity assay confirmed the stability of the antigen after conjugation. After three nasal immunizations, the H1N1-TMC/NP induced significantly higher levels of serum IgG and mucosal sIgA compared with free antigen. A hemagglutination inhibition assay showed that H1N1-TMC/NP induced much more protective antibodies than antigen-encapsulated nanoparticles or alum-precipitated antigen (I.M.). In the mechanistic study, H1N1-TMC/NP was shown to stimulate macrophages to produce IL-1β and IL-6 and to stimulate spleen lymphocytes to produce IL-2 and IFN-γ. These results indicated that H1N1-TMC/NP may be an effective vaccine against influenza A (H1N1) viruses for use in nasal immunization.
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, P. R. China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, P. R. China.
authors.forename: Xiaoyao
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, P. R. China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, P. R. China.
authors.forename: Xiayan
authors.initials: X
authors.lastname: Shao
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, P. R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, P. R. China.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, P. R. China.
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D000956:Antigens, Viral / Q000008:administration & dosage* / Q000276:immunology*; D048271:Chitosan / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004337:Drug Carriers / Q000008:administration & dosage*; D005260:Female; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D008689:Methacrylates / Q000008:administration & dosage*; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D004337:Drug Carriers; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D008689:Methacrylates; C000601247:N-trimethylaminoethylmethacrylate chitosan; D048271:Chitosan
keywords: TMC; conjugated; influenza A (H1N1); nanoparticles; nasal vaccination