期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 158, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2022.114170
关键词
Antibody; Immunotherapy; PCSK9; Toxicity; Vaccine
The antiPCSK9 vaccine is safe and does not have adverse effects on the function of different organs and blood levels of cellular and biochemical biomarkers in healthy mice.
Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a novel cholesterol-lowering treatment for decreasing the risk of atherosclerosis. We have previously shown that active immunization using the antiPCSK9 vaccine could decrease hypercholesterolemia and impede the development of atheroscle-rotic lesions in the experimental model of atherosclerosis. Here, we evaluated the toxicity of the vaccine in healthy mice.Methods: Forty male and female albino mice were divided into 4 experimental groups, including vaccine female (10 mice) and male (10 mice) groups receiving the antiPCSK9 vaccine as well as the corresponding control fe-male (10 mice) and male (10 mice) groups receiving the phosphate buffer. Vaccination was planned based on 4 subcutaneous injections of the vaccine formulation (10 mu g/mouse) in bi-weekly intervals. The toxicity study was performed by the subacute protocol, 28 days after the last vaccine injection. To this end, the plasma levels of lipid indexes, urea, creatinine, AST, ALT, ALP, and fasting plasma glucose (FPG), as well as the CBC test were measured. To evaluate histopathological alterations, various tissues including the heart, liver, kidney, spleen, and brain were studied using hematoxylin & eosin (H&E) staining by an expert pathologist. The severity of damage to the tissue was considered based on the standard classification; grade 1 as light damage, grade 2 as moderate damage, grade 3 as near intense damage, and grade 4 as intense damage.Results: The results showed non-significant changes of total cholesterol, LDL-C, triglyceride, HDL-C, FBS, creat-inine, urea, AST, ALP, ALT, and PAB in the vaccinated mice when compared with control mice. The CBS test indicated that there were no significant changes in the levels of WBC, RBC, HGB, HCT, MCH, MCHC, PLT, LYM, NEUT, MCV, RDW-S, PDW, and MPV in the vaccinated mice when compared with control mice. Evaluating histopathological alterations in various tissues indicated no significant adverse effects in vaccinated mice when compared to control mice.Conclusion: The findings of the present study indicate that antiPCSK9 is safe and exerts no adverse effects on the function of different organs and blood levels of cellular and biochemical biomarkers in healthy mice.
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