Estimating the best PCSK9 vaccine design for atherosclerosis based on mouse models: A frequentist network meta-analysis

Authors

  • Muhammad Iqhrammullah Postgraduate School of Public Health, Universitas Muhammadiyah Aceh, Banda Aceh, Indonesia
  • Asyraf Muzaffar School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
  • Derren David Christian Homenta Rampengan Faculty of Medicine, Universitas Sam Ratulangi, Manado, Indonesia
  • Chairul Ichwan Intern at Department of Cardiology and Vascular Medicine, Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia
  • Ayers Gilberth Ivano Kalaij Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • Seba Talat Al-Gunaid School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
  • Nur Adiba Purba Department of Cardiology and Vascular Medicine, Dr. Soetomo Hospital, Faculty of Medicine, University of Airlangga, Surabaya, Indonesia
  • Muhammad Rinaldi Sufri Directoral General of Disease Control and Prevention, Ministry of Health, Jakarta, Indonesia
  • Adi Purnawarman Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia; Department of Cardiology and Vascular Medicine, Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia
  • Naufal Gusti Postgraduate School of Public Health, Universitas Muhammadiyah Aceh, Banda Aceh, Indonesia

DOI:

https://doi.org/10.21542/gcsp.2025.19

Abstract

Background: Proprotein convertase subtilisin/kexin 9 (PCSK9) plays a crucial role in regulating the plasma levels of low-density lipoprotein cholesterol (LDL-C) and low-density lipoprotein receptor (LDLR). In contrast, vaccines have been developed to induce PCSK9-specific antibodies, which could improve dyslipidemia in atherosclerotic animal models. The aim of this study was to determine the best PCSK9 vaccine design for improving dyslipidemia and atherosclerosis in animal studies.

Methods: A systematic search was performed on PubMed, Scopus, and Web of Science for studies published as of August 2024. Studies that developed a PCSK9 vaccine and reported its efficacy in mouse models were included. A random-effects model was used to conduct a frequentist network meta-analysis. The standardized mean difference (SMD) and 95% confidence interval (CI) were used as size effects. Heterogeneity in the model was judged based on the I2 values.

Results: Six studies, published between 2014 and 2024, were included. There were 8 vaccine designs developed using different peptides, carriers, and delivery systems. Vaccines prepared with human PCSK9-003 epitope peptide (F-A-Q-S-I-P-W-N) with Qb virus-like particles consistently appeared to be the best vaccine design for the reduction of total cholesterol (p<0.001), LDL-C (p=0.002), and triglycerides (p=0.024). The heterogeneity was low for total cholesterol and LDL-C (I2 = 16% and 0%, respectively) and moderate for triglycerides (I2 =64%).

Conclusion: Vaccines prepared from the PCSK9-003 epitope peptide (F-A-Q-S-I-P-W-N) conjugated with Qb virus-like particles are suggested to be promising for atherosclerosis treatment by reducing LDL-C and improving other lipid profiles.

PROSPERO: CRD42024596892.

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Published

2025-05-21

Issue

Vol. 2025 No. 2 (2025)

Section

Review articles

License

Copyright (c) 2025 Muhammad Iqhrammullah, Asyraf Muzaffar, Derren David Christian Homenta Rampengan, Chairul Ichwan, Ayers Gilberth Ivano Kalaij, Seba Talat Al-Gunaid, Nur Adiba Purba, Muhammad Rinaldi Sufri, Adi Purnawarman, Naufal Gusti

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This work is licensed under a Creative Commons Attribution 4.0 International License.

This is an open access article distributed under the terms of the Creative Commons Attribution license CC BY 4.0, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.