Vaccination against GIP for the treatment of obesity.
BACKGROUND
According to the WHO, more than 1 billion people worldwide are overweight and at risk of developing chronic illnesses, including cardiovascular disease, type 2 diabetes, hypertension and stroke. Current therapies show limited efficacy and are often associated with unpleasant side-effect profiles, hence there is a medical need for new therapeutic interventions in the field of obesity. Gastric inhibitory peptide (GIP, also known as glucose-dependent insulinotropic polypeptide) has recently been postulated to link over-nutrition with obesity. In fact GIP receptor-deficient mice (GIPR(-/-)) were shown to be completely protected from diet-induced obesity. Thus, disrupting GIP signaling represents a promising novel therapeutic strategy for the treatment of obesity.


RESULTS
In order to block GIP signaling we chose an active vaccination approach using GIP peptides covalently attached to virus-like particles (VLP-GIP). Vaccination of mice with VLP-GIP induced high titers of specific antibodies and efficiently reduced body weight gain in animals fed a high fat diet. The reduction in body weight gain could be attributed to reduced accumulation of fat. Moreover, increased weight loss was observed in obese mice vaccinated with VLP-GIP. Importantly, despite the incretin action of GIP, VLP-GIP-treated mice did not show signs of glucose intolerance.


CONCLUSIONS
This study shows that vaccination against GIP was safe and effective. Thus active vaccination may represent a novel, long-lasting treatment for obesity. However further preclinical safety/toxicology studies will be required before the therapeutic concept can be addressed in humans.
Fulurija
Alma
A
Cytos Biotechnology AG, Schlieren, Switzerland.
Lutz
Thomas A
TA
Sladko
Katja
K
Osto
Melania
M
Wielinga
Peter Y
PY
Bachmann
Martin F
MF
Saudan
Philippe
P
D016475:3T3 Cells; D000818:Animals; D001835:Body Weight; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005749:Gastric Inhibitory Polypeptide / Q000737:chemistry* / Q000276:immunology; D006706:Homeostasis; D006801:Humans; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000378:metabolism* / Q000628:therapy*; D015398:Signal Transduction; D014612:Vaccines / Q000737:chemistry*
D014612:Vaccines; D005749:Gastric Inhibitory Polypeptide
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