The Immunogenic Potential of PCSK9 Peptide Vaccine in Mice

Author:

Sahebkar Amirhossein123,Ataei Sarina14,Momtazi-Borojeni Amir Abbas5,Ganjali Shiva6,Banach Maciej78

Affiliation:

1. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

2. Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3. Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

4. Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran

5. Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran

6. Department of Medical Biotechnology and Nanotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

7. Department of Preventive Cardiology and Lipidology, Medical University of Lodz, 93-338Lodz, Poland

8. Cardiovascular Research Centre, University of Zielona Gora, 65-046 Zielona Gora, Poland

Abstract

Aim: To evaluate the immunogenic potential of the carrier-free peptide-based anti-PCSK9 (proprotein convertase subtilisin/kexin 9) vaccine in albino mice. Methods: The immunogenic pcsk9 peptide and 0.4% alum adjuvant were mixed thoroughly at a 1:1 ratio and used as a vaccine formulation. To assess the humoral immune response, animals' blood was sampled two weeks after the last immunization. The ELISA method was employed to measure serum anti-PCSK9 antibody titers, PCSK9 concentrations, and PCSK9/LDLR interaction. Results: ELISA analysis showed significant induction of IgG antibody titers by PCSK9 peptide vaccine in vaccinated mice sera compared to the control mice (in male and female mice were 12000±586 and 11566±642, respectively, p<0.001). Mechanistic analyses showed a significant reduction in serum PCSK9 concentrations by vaccine-induced antibodies in vaccine groups compared to the control groups (in male mice by 29±5 ng/mL (22.4%), p<0.001 and female mice by 26±5 ng / mL (21.0%), p<0.001). Serum concentrations of PCSK9 in control and vaccine groups were 131±8.6 ng / mL and 102±8.1 ng/ml in male mice and 124±6 ng/ml and 98±10 ng/ml in female mice, respectively. Moreover, vaccine-induced antibodies inhibited the PCSK9-LDLR interaction in male and female groups by 34% and 26%, respectively. No significant difference was detected between the male and female groups in all tests (p>0.05). Conclusions: According to our results, the PCSK9 peptide vaccine provoked the humoral immune system in albino mice to produce functional antibodies that inhibit plasma PCSK9. These effects were seen in both genders without any significant difference.

Publisher

Bentham Science Publishers Ltd.

Subject

Pharmacology,Molecular Medicine,Drug Discovery,Biochemistry,Organic Chemistry

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