title: Nanogel-based pneumococcal surface protein A nasal vaccine induces microRNA-associated Th17 cell responses with neutralizing antibodies against Streptococcus pneumoniae in macaques.
abstract: We previously established a nanosized nasal vaccine delivery system by using a cationic cholesteryl group-bearing pullulan nanogel (cCHP nanogel), which is a universal protein-based antigen-delivery vehicle for adjuvant-free nasal vaccination. In the present study, we examined the central nervous system safety and efficacy of nasal vaccination with our developed cCHP nanogel containing pneumococcal surface protein A (PspA-nanogel) against pneumococcal infection in nonhuman primates. When [(18)F]-labeled PspA-nanogel was nasally administered to a rhesus macaque (Macaca mulatta), longer-term retention of PspA was noted in the nasal cavity when compared with administration of PspA alone. Of importance, no deposition of [(18)F]-PspA was seen in the olfactory bulbs or brain. Nasal PspA-nanogel vaccination effectively induced PspA-specific serum IgG with protective activity and mucosal secretory IgA (SIgA) Ab responses in cynomolgus macaques (Macaca fascicularis). Nasal PspA-nanogel-induced immune responses were mediated through T-helper (Th) 2 and Th17 cytokine responses concomitantly with marked increases in the levels of miR-181a and miR-326 in the serum and respiratory tract tissues, respectively, of the macaques. These results demonstrate that nasal PspA-nanogel vaccination is a safe and effective strategy for the development of a nasal vaccine for the prevention of pneumonia in humans.
authors: Division of Mucosal Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
authors: Y
authors: Y
authors: Fukuyama
authors: 1] Division of Mucosal Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan [2] International Research and Development Center for Mucosal Vaccine, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
authors: Y
authors: Y
authors: Yuki
authors: Corporation for Production and Research of Laboratory Primates, Tsukuba, Ibaraki, Japan.
authors: Y
authors: Y
authors: Katakai
authors: PET Center, Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan.
authors: N
authors: N
authors: Harada
authors: Department of Polymer Chemistry, Kyoto University Graduate School of Engineering, Nishikyo-ku, Kyoto, Japan.
authors: H
authors: H
authors: Takahashi
authors: Department of Polymer Chemistry, Kyoto University Graduate School of Engineering, Nishikyo-ku, Kyoto, Japan.
authors: S
authors: S
authors: Takeda
authors: Division of Mucosal Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
authors: M
authors: M
authors: Mejima
authors: Division of Mucosal Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
authors: S
authors: S
authors: Joo
authors: Division of Mucosal Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
authors: S
authors: S
authors: Kurokawa
authors: Department of Polymer Chemistry, Kyoto University Graduate School of Engineering, Nishikyo-ku, Kyoto, Japan.
authors: S
authors: S
authors: Sawada
authors: Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki, Japan.
authors: H
authors: H
authors: Shibata
authors: Division of Mucosal Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
authors: E J
authors: EJ
authors: Park
authors: Departments of Pediatric Dentistry and Microbiology, The Immunobiology Vaccine Center, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors: K
authors: K
authors: Fujihashi
authors: Department of Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors: D E
authors: DE
authors: Briles
authors: Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki, Japan.
authors: Y
authors: Y
authors: Yasutomi
authors: PET Center, Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan.
authors: H
authors: H
authors: Tsukada
authors: Department of Polymer Chemistry, Kyoto University Graduate School of Engineering, Nishikyo-ku, Kyoto, Japan.
authors: K
authors: K
authors: Akiyoshi
authors: 1] Division of Mucosal Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan [2] International Research and Development Center for Mucosal Vaccine, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
authors: H
authors: H
authors: Kiyono
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology / Q000494:pharmacology*; D004337:Drug Carriers / Q000494:pharmacology*; D005260:Female; D005782:Gels; D005936:Glucans / Q000494:pharmacology*; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D035683:MicroRNAs / Q000276:immunology*; D053758:Nanoparticles; D011018:Pneumonia, Pneumococcal / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D013296:Streptococcus pneumoniae / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D001426:Bacterial Proteins; D004337:Drug Carriers; D005782:Gels; D005936:Glucans; D035683:MicroRNAs; C051592:pneumococcal surface protein A; C009109:pullulan