Mucosal Immunology advance online publication 25 January 2017; doi: 10.1038/mi.2016.137

Nanogel-based nasal ghrelin vaccine prevents obesity

T Azegami1,2,3, Y Yuki2,3, S Sawada4,5, M Mejima2, K Ishige6, K Akiyoshi4,5, H Itoh1 and H Kiyono2,3

  1. 1Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan
  2. 2Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  3. 3International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  4. 4Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Kyoto, Japan
  5. 5Japan Science and Technology Agency (JST), The Exploratory Research for Advanced Technology (ERATO), Katura Int’ Tech Center, Kyoto, Japan
  6. 6Biochemicals Division, Yamasa Corporation, Chiba, Japan

Correspondence: T Azegami or H Kiyono, ( or (

Received 23 June 2016; Accepted 19 December 2016
Advance online publication 25 January 2017



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.

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