title: Nanogel-based PspA intranasal vaccine prevents invasive disease and nasal colonization by Streptococcus pneumoniae.
abstract: To establish a safer and more effective vaccine against pneumococcal respiratory infections, current knowledge regarding the antigens common among pneumococcal strains and improvements to the system for delivering these antigens across the mucosal barrier must be integrated. We developed a pneumococcal vaccine that combines the advantages of pneumococcal surface protein A (PspA) with a nontoxic intranasal vaccine delivery system based on a nanometer-sized hydrogel (nanogel) consisting of a cationic cholesteryl group-bearing pullulan (cCHP). The efficacy of the nanogel-based PspA nasal vaccine (cCHP-PspA) was tested in murine pneumococcal airway infection models. Intranasal vaccination with cCHP-PspA provided protective immunity against lethal challenge with Streptococcus pneumoniae Xen10, reduced colonization and invasion by bacteria in the upper and lower respiratory tracts, and induced systemic and nasal mucosal Th17 responses, high levels of PspA-specific serum immunoglobulin G (IgG), and nasal and bronchial IgA antibody responses. Moreover, there was no sign of PspA delivery by nanogel to either the olfactory bulbs or the central nervous system after intranasal administration. These results demonstrate the effectiveness and safety of the nanogel-based PspA nasal vaccine system as a universal mucosal vaccine against pneumococcal respiratory infection.
authors: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors: Il Gyu
authors: IG
authors: Kong
authors: Ayuko
authors: A
authors: Sato
authors: Yoshikazu
authors: Y
authors: Yuki
authors: Tomonori
authors: T
authors: Nochi
authors: Haruko
authors: H
authors: Takahashi
authors: Shinichi
authors: S
authors: Sawada
authors: Mio
authors: M
authors: Mejima
authors: Shiho
authors: S
authors: Kurokawa
authors: Kazunari
authors: K
authors: Okada
authors: Shintaro
authors: S
authors: Sato
authors: David E
authors: DE
authors: Briles
authors: Jun
authors: J
authors: Kunisawa
authors: Yusuke
authors: Y
authors: Inoue
authors: Masafumi
authors: M
authors: Yamamoto
authors: Kazunari
authors: K
authors: Akiyoshi
authors: Hiroshi
authors: H
authors: Kiyono
mesh_terms: D056704:Adaptive Immunity; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D000080385:Nanogels; D009666:Nose / Q000382:microbiology*; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D000080385:Nanogels; D022242:Pneumococcal Vaccines; C051592:pneumococcal surface protein A; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine