title: Intranasal Immunization Using Mannatide as a Novel Adjuvant for an Inactivated Influenza Vaccine and Its Adjuvant Effect Compared with MF59.
abstract: Intranasal vaccination is more potent than parenteral injection for the prevention of influenza. However, because the poor efficiency of antigen uptake across the nasal mucosa is a key issue, immunostimulatory adjuvants are essential for intranasal vaccines. The immunomodulator mannatide or polyactin (PA) has been used for the clinical treatment of impaired immunity in China, but its adjuvant effect on an inactivated trivalent influenza vaccine (ITIV) via intranasal vaccination is unclear. To explore the adjuvant effect of PA, an inactivated trivalent influenza virus with or without PA or MF59 was instilled intranasally once a week in BALB/c mice. Humoral immunity was assessed by both the ELISA and hemagglutination inhibition (HI) methods using antigen-specific antibodies. Splenic lymphocyte proliferation and the IFN-γ level were measured to evaluate cell-mediated immunity. The post-vaccination serum HI antibody geometric mean titers (GMTs) for the H1N1 and H3N2 strains, antigen-specific serum IgG and IgA GMTs, mucosal SIgA GMT, splenic lymphocyte proliferation, and IFN-γ were significantly increased in the high-dose PA-adjuvanted vaccine group. The seroconversion rate and the mucosal response for the H3N2 strain were significantly elevated after high-dose PA administration. These adjuvant effects of high-dose PA for the influenza vaccine were comparable with those of the MF59 adjuvant, and abnormal signs or pathological changes were not found in the evaluated organs. In conclusion, PA is a novel mucosal adjuvant for intranasal vaccination with the ITIV that has safe and effective mucosal adjuvanticity in mice and successfully induces both serum and mucosal antibody responses and a cell-mediated response.
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors.forename: Shu-Ting
authors.initials: ST
authors.lastname: Ren
authors.affiliation: No. 6 Vaccine Workshop, Changchun Institute of Biological Products Co., Ltd., Changchun, China.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Zhang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.|Department of Pathology, Xi'an City Center Hospital, Xi'an, China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Sun
authors.affiliation: Reagent R&D Dep. Scientific Research Management Center, Capital Bio Technology, Beijing, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Sun
authors.affiliation: No. 6 Vaccine Workshop, Changchun Institute of Biological Products Co., Ltd., Changchun, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: No. 6 Vaccine Workshop, Changchun Institute of Biological Products Co., Ltd., Changchun, China.
authors.forename: Qi-Yuan
authors.initials: QY
authors.lastname: Guo
authors.affiliation: No. 6 Vaccine Workshop, Changchun Institute of Biological Products Co., Ltd., Changchun, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Changchun Institute of Biological Products Co., Ltd., Changchun, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Guo
authors.affiliation: Therapeutic Vaccines Engineering Center of Shaanxi Province, Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Che
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.|Therapeutic Vaccines Engineering Center of Shaanxi Province, Xi'an Jiaotong University Health Science Center, Xi'an, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xi'an Medical University Health Science Center, Xi'an, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000281:Administration, Intranasal; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation; D000956:Antigens, Viral / Q000276:immunology; D049109:Cell Proliferation; D000939:Epitopes / Q000276:immunology; D005260:Female; D006020:Glycopeptides / Q000008:administration & dosage / Q000276:immunology*; D006385:Hemagglutination Inhibition Tests; D007111:Immunity, Cellular; D007114:Immunization; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007252:Influenza Vaccines / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000473:pathology; D011136:Polysorbates / Q000008:administration & dosage / Q000627:therapeutic use*; D013154:Spleen / Q000166:cytology; D013185:Squalene / Q000008:administration & dosage / Q000627:therapeutic use*; D014132:Trachea / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D000956:Antigens, Viral; D000939:Epitopes; D006020:Glycopeptides; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene; D007371:Interferon-gamma; C064233:polyactin A