Efficacy and safety in mice of repeated, lifelong administration of an ANGPTL3 vaccine

Abstract Previously, we reported that an ANGPTL3 vaccine is a hopeful therapeutic option against dyslipidemia. In our current study, we assess durability and booster effects of that vaccine over a period representing a mouse’s lifespan. The vaccine remained effective for over one year, and booster vaccination maintained suppression of circulating triglyceride levels thereafter without major adverse effects on lungs, kidneys, or liver, suggesting vaccine efficacy and safety

Association between circulating ANGPTL levels and general medical status (n = 800).

<p>A generalized linear model was used. All variables listed were included in the model. ANGPTL, Angiopoietin-like protein; β, regression coefficient; 95% CI, 95% confidence interval; P, probability; and CKD, chronic kidney disease.</p

Association between circulating ANGPTL8 levels and laboratory tests relevant to obesity, impaired glycometabolism, or dyslipidemia (n = 800).

<p>A generalized linear model was used. To evaluate BMI, each covariate was adjusted by all variables listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193731#pone.0193731.t003" target="_blank">Table 3</a>, minus obesity. To evaluate HbA1C or glucose, each covariate was adjusted by all variables listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193731#pone.0193731.t003" target="_blank">Table 3</a>, minus the impaired glycometabolism catergory. To evaluate HDL, LDL or triglyceride, each covariate was adjusted by all variables listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193731#pone.0193731.t003" target="_blank">Table 3</a>, minus the dyslipidemia category. BMI, body mass index; HbA1C, hemoglobin A1C; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; TG, triglyceride; β, regression coefficient; and 95% CI, 95% confidence interval.</p

Association of circulating ANGPTL 3, 4, and 8 levels with medical status in a population undergoing routine medical checkups: A cross-sectional study - Fig 1

<p>Distribution of circulating levels of (A) ANGPTL3, (B) ANGPTL4, and (C) ANGPTL8. IQR, Interquartile range (n = 988).</p

Association between circulating ANGPTL4 levels and laboratory tests relevant to impaired glycometabolism, hepatic impairment or inflammation (n = 800).

<p>A generalized linear model was used. To evaluate HbA_1C or glucose, each covariate was adjusted by all variables listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193731#pone.0193731.t003" target="_blank">Table 3</a>, minus the impaired glyometabolism category. To evaluate AST, ALT, or GGT, each covariate was adjusted by all variables listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193731#pone.0193731.t003" target="_blank">Table 3</a>, minus the hepatic impairment category. To evaluate hs-CRP, each covariate was adjusted by all variables listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193731#pone.0193731.t003" target="_blank">Table 3</a>, minus inflammation. β, regression coefficient; 95% CI, 95% confidence interval; HbA_1C, hemoglobin A_1C; AST, aspartate transaminase; ALT, alanine transaminase; GGT, Gamma-glutamyltransferase; and hs-CRP, high sensitivity C reactive protein.</p

Association between circulating ANGPTL3 levels and lab values relevant to hepatic impairment or inflammation (n = 800).

<p>A generalized linear model was used. To evaluate AST, ALT or GGT, covariates were adjusted by all variables listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193731#pone.0193731.t003" target="_blank">Table 3</a>, minus the hepatic impairment category. To evaluate hs-CRP, covariates were adjusted by all variables listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193731#pone.0193731.t003" target="_blank">Table 3</a>, minus the inflammation category. β, regression coefficient; 95% CI, 95% confidence interval; AST, aspartate transaminase; ALT, alanine transaminase; GGT, gamma-glutamyltransferase; and hs-CRP, high sensitivity C reactive protein.</p