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

10 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

Fingerprint

Ghrelin
Nose
Vaccines
Obesity
Antigens
Energy Metabolism
Recombinant Fusion Proteins
Pneumococcal Vaccines
Brown Adipose Tissue
Hydrogel
Weight Gain
NanoGel
Comorbidity
Immunization
Carrier Proteins
Cardiovascular Diseases
Eating
Immunoglobulin G
Fats
Body Weight

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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

Nanogel-based nasal ghrelin vaccine prevents obesity. / Azegami, Tatsuhiko; Yuki, Y.; Sawada, S.; Mejima, M.; Ishige, K.; Akiyoshi, K.; Itoh, Hiroshi; Kiyono, H.

In: Mucosal Immunology, Vol. 10, No. 5, 01.09.2017, p. 1351-1360.

Research output: Contribution to journalArticle

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, vol. 10, no. 5, pp. 1351-1360. https://doi.org/10.1038/mi.2016.137
Azegami T, Yuki Y, Sawada S, Mejima M, Ishige K, Akiyoshi K et al. Nanogel-based nasal ghrelin vaccine prevents obesity. Mucosal Immunology. 2017 Sep 1;10(5):1351-1360. https://doi.org/10.1038/mi.2016.137
Azegami, Tatsuhiko ; Yuki, Y. ; Sawada, S. ; Mejima, M. ; Ishige, K. ; Akiyoshi, K. ; Itoh, Hiroshi ; Kiyono, H. / Nanogel-based nasal ghrelin vaccine prevents obesity. In: Mucosal Immunology. 2017 ; Vol. 10, No. 5. pp. 1351-1360.
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