Nanogel-based nasal ghrelin vaccine prevents obesity

Tatsuhiko Azegami, Y. Yuki, S. Sawada, M. Mejima, K. Ishige, K. Akiyoshi, Hiroshi Itoh, H. Kiyono

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1351-1360
Number of pages10
JournalMucosal Immunology
Volume10
Issue number5
DOIs
Publication statusPublished - 2017 Sep 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Azegami, T., Yuki, Y., Sawada, S., Mejima, M., Ishige, K., Akiyoshi, K., Itoh, H., & Kiyono, H. (2017). Nanogel-based nasal ghrelin vaccine prevents obesity. Mucosal Immunology, 10(5), 1351-1360. https://doi.org/10.1038/mi.2016.137