Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Immunization using ApoB-100 peptide–linked nanoparticles reduces atherosclerosis
Kuang-Yuh Chyu, … , Eun Ji Chung, Prediman K. Shah
Kuang-Yuh Chyu, … , Eun Ji Chung, Prediman K. Shah
Published May 10, 2022
Citation Information: JCI Insight. 2022;7(11):e149741. https://doi.org/10.1172/jci.insight.149741.
View: Text | PDF
Research Article Cardiology Vaccines

Immunization using ApoB-100 peptide–linked nanoparticles reduces atherosclerosis

  • Text
  • PDF
Abstract

Active immunization with the apolipoprotein B-100 (ApoB-100) peptide P210 reduces experimental atherosclerosis. To advance this immunization strategy to future clinical testing, we explored the possibility of delivering P210 as an antigen using nanoparticles, given this approach has been used clinically. We first characterized the responses of T cells to P210 using PBMCs from patients with atherosclerotic cardiovascular disease (ASCVD). We then investigated the use of P210 in self-assembling peptide amphiphile micelles (P210-PAMs) as a vaccine formulation to reduce atherosclerosis in B6.129P2-Apoetm1Unc/J (ApoE–/–) mice and P210’s potential mechanisms of action. We also generated and characterized a humanized mouse model with chimeric HLA-A*02:01/Kb in ApoE–/– background to test the efficacy of P210-PAM immunization as a bridge to future clinical testing. P210 provoked T cell activation and memory response in PBMCs of patients with ASCVD. Dendritic cell uptake of P210-PAM and its costaining with MHC-I molecules supported its use as a vaccine formulation. In ApoE–/– mice, immunization with P210-PAMs dampened P210-specific CD4+ T cell proliferative response and CD8+ T cell cytolytic response, modulated macrophage phenotype, and significantly reduced aortic atherosclerosis. Potential clinical relevance of P210-PAM immunization was demonstrated by reduced atherosclerosis in the humanized ApoE–/– mouse model. Our data support experimental and translational use of P210-PAM as a potential vaccine candidate against human ASCVD.

Authors

Kuang-Yuh Chyu, Xiaoning Zhao, Jianchang Zhou, Paul C. Dimayuga, Nicole W.M. Lio, Bojan Cercek, Noah T. Trac, Eun Ji Chung, Prediman K. Shah

×

Figure 7

ApoBKTTKQSFDL pentamer.

Options: View larger image (or click on image) Download as PowerPoint
ApoBKTTKQSFDL pentamer.
(A) Binding scores of P210 epitope sequences lis...
(A) Binding scores of P210 epitope sequences listed in Table 2 from REVEAL binding assay. Representative plot of PBMCs from an HLA-A*02:01+ volunteer stained with (B) HLA-A*02:01 control pentamer or (C) ApoBKTTKQSFDL pentamer, (D) with backgating in magenta. (E) ApoBKTTKQSFDL pentamer+CD8+ T cells in PBMCs of HLA-A*02:01+ volunteers compared with control HLA-A*02:01 pentamer (n = 10). (F) Aliquots available from 8 of the same volunteers were stimulated with 20 μg/mL P210 peptide or vehicle (sterile double-distilled H2O) for 5 days. Representative scatterplot of vehicle (G) or P210 peptide (H) sample stained with ApoBKTTKQSFDL pentamer. (I) The P210-stimulated samples were also stained with HLA-A*02:01 control pentamer as reference for pentamer specificity. *P < 0.05 by 2-tailed t test.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts