title: Nanogel-based nasal ghrelin vaccine prevents obesity.
abstract: Obesity is associated with multiple comorbidities such as cardiovascular diseases and has a huge economic impact on the health-care system. However, the treatment of obesity remains insufficient in terms of efficacy, tolerability, and safety. Here we created a nasal vaccine against obesity for the first time. To avoid the injectable administration-caused pain and skin-related adverse event, we focused on the intranasal route of antigen delivery. We developed a vaccine antigen (ghrelin-PspA (pneumococcal surface protein A)), which is a recombinant fusion protein incorporating ghrelin, a hormone that stimulates food intake and decreases energy expenditure, and PspA, a candidate of pneumococcal vaccine as a carrier protein. Ghrelin-PspA antigen was mixed with cyclic di-GMP adjuvant to enhance the immunogenicity and incorporated within a nanometer-sized hydrogel for the effective antigen delivery. Intranasal immunization with ghrelin-PspA vaccine elicited serum immunoglobulin G antibodies against ghrelin and attenuated body weight gain in diet-induced obesity mice. This obesity-attenuating effect was caused by a decrease in fat accumulation and an increase in energy expenditure that was partially due to an increase in the expression of mitochondrial uncoupling protein 1 in brown adipose tissue. The development of this nasal vaccine provides a new strategy for the prevention and treatment of obesity.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.|Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.|International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Azegami
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.|International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yuki
authors.affiliation: Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Kyoto, Japan.|Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Katura Int' Tech Center, Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sawada
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Mejima
authors.affiliation: Biochemicals Division, Yamasa Corporation, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ishige
authors.affiliation: Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Kyoto, Japan.|Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Katura Int' Tech Center, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Akiyoshi
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Itoh
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.|International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation; D001426:Bacterial Proteins / Q000235:genetics*; D001835:Body Weight; D004035:Diet Therapy; D004195:Disease Models, Animal; D005782:Gels / Q000008:administration & dosage*; D054439:Ghrelin / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage*; D009765:Obesity / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D014612:Vaccines / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D005782:Gels; D054439:Ghrelin; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D014612:Vaccines; C051592:pneumococcal surface protein A