title: Compound 48/80 acts as a potent mucosal adjuvant for vaccination against Streptococcus pneumoniae infection in young mice.
abstract: Streptococcus pneumoniae, a major respiratory pathogen, is a leading cause of death among children worldwide. Mucosal vaccination is a recommended method to prevent respiratory infection. However, development of mucosal vaccination is usually hindered due to the lack of safe and effective mucosal adjuvants. Mast cell activator compound 48/80 (C48/80) has been used as a mucosal adjuvant in immunization of adult mice, but its adjuvanticity is not clear in the immunization of young mice. In this study, the adjuvanticity of C48/80 was evaluated when intranasally co-administrated with a pneumococcal vaccine candidate strain SPY1 in a young mice model in comparison with a classical mucosal adjuvant cholera toxin (CT) and a relatively safe mucosal adjuvant Pam2CSK4. All three adjuvants enhanced antibody responses, whereas serum IgG titers were maintained at a stable level during the 3 months after the last immunization only in the SPY1+C48/80 and SPY1+CT groups. Furthermore, both the SPY1+CT group and the SPY1+C48/80 group induced strong Th17 immune response. Notably, C48/80 showed the exceptional ability to promote the clearance of nasal pneumococcal colonization which CT and Pam2CSK4 did not show. We found that C48/80's ability to induce protection against nasal pneumococcal colonization depended on B cells and IL-17A. Additionally, C48/80, as a mucosal adjuvant, showed a greater ability to protect young mice against lethal pneumococcal infection than CT. In comparison with CT, C48/80 also showed a favorable safety. These results reveal a promising perspective for using C48/80 as a mucosal adjuvant to improve protection against pneumococcal diseases early in life.
authors.affiliation: College of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, China; Department of Clinical Laboratory, Chengdu Women's and Children's Central Hospital, Chengdu 610091, China.
authors.forename: Lingbin
authors.initials: L
authors.lastname: Zeng
authors.affiliation: College of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yusi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, The 3rd People's Hospital of Chongqing, Chongqing 400014, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Liao
authors.affiliation: College of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Song
authors.affiliation: College of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, China.
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.affiliation: College of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: College of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Yin
authors.affiliation: College of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, China. Electronic address: xuwen0303@126.com.
authors.forename: Wenchun
authors.initials: W
authors.lastname: Xu
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D018928:Immunity, Mucosal; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D009092:Mucous Membrane / Q000276:immunology* / Q000382:microbiology; D011008:Pneumococcal Infections / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D003189:p-Methoxy-N-methylphenethylamine / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D016207:Cytokines; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; D003189:p-Methoxy-N-methylphenethylamine
keywords: Mucosal adjuvant; Nasal colonization; Protective immunity; Streptococcus pneumoniae