Abstract
The purpose of the study was to test the therapeutic effects of novel vaccines for reducing weight gain and increasing weight loss in diet induced obesity (DIO) model. Male C57BL/6 J mice, fed a 60% Kcal fat diet for 8 weeks prior to the start of the study, were vaccinated via the intraperitoneal route with two formulations (JH17 & JH18) of chimeric-somatostatin vaccines at 1 and 22 days of the study. Control mice were injected with PBS. All mice continued to be feed the 60% Kcal fat diet for the 6 week study. Body weights were measured two times a week and food intake was measured weekly. At week 6, mice were euthanized and a terminal bleed was made and antibody levels to somatostatin and levels of insulin-like growth factor 1 (IGF-1) were determined. Vaccination with both vaccine formulations induced a statistically significant body weight change over the study period, as compared with PBS controls. Percentage of baseline body weight was also significantly affected by vaccination during the study period. Vaccinates finished the study at 104% and 107% of baseline weight, JH17 & JH18 respectively, while untreated controls reached 115% of baseline weight. Food intake per mouse was similar in all mouse groups during the entire study. Control mice did not demonstrate any antibody titers to somatostatin, while all vaccinated mice had measurable antibody responses (> 1:500,000 titer). IGF-1 levels were not statistically significant among the groups, but were elevated in the JH18 vaccinates (mean 440.4 ng/mL) when compared with PBS controls (mean 365.6 ng/mL). Vaccination with either JH17 or JH18 chimeric -somatostatin vaccines produced a statistically significant weight loss as compared with PBS controls (P < 0.0001), even though the DIO mice with continually fed a 60% Kcal fat diet. The weight loss/lower weight gain observations were even more significant, as all mice consumed similar amounts of food for the entire study. The presence of high levels of anti-somatostatin antibodies at 6 weeks was correlative with the weight observations and confirmed the success of vaccination.