Vaccination against T-cell epitopes of native ApoB100 reduces vascular inflammation and disease in a humanized mouse model of atherosclerosis

J Intern Med. 2017 Apr;281(4):383-397. doi: 10.1111/joim.12589. Epub 2017 Feb 13.


Background and objectives: The T-cell response to low-density lipoprotein (LDL) in the vessel wall plays a critical role in atherosclerotic plaque formation and stability. In this study, we used a new translational approach to investigate epitopes from human apolipoprotein B100 (ApoB100), the protein component of LDL, which triggers T-cell activation. We also evaluated the potential of two selected native ApoB100 epitopes to modulate atherosclerosis in human ApoB100-transgenic Ldlr-/- (HuBL) mice.

Methods and results: HuBL mice were immunized with human atherosclerotic plaque homogenate to boost cellular autoimmune response to tissue-derived ApoB100 epitopes. In vitro challenge of splenocytes from immunized mice with a library of overlapping native peptides covering human ApoB100 revealed several sequences eliciting T-cell proliferation. Of these sequences, peptide (P) 265 and P295 were predicted to bind several human leucocyte antigen (HLA) haplotypes and induced high levels of interferon (IFN)-γ. Vaccination of HuBL mice with these peptides mounted a strong adaptive immune response to native ApoB100, including high levels of epitope-specific plasma IgGs. Interestingly, P265 and P295 vaccines significantly decreased plaque size, reduced macrophage infiltration and increased IgG1 deposition in the plaques. Purified IgGs from vaccinated mice displayed anti-inflammatory properties against macrophages in vitro, reducing their response to LPS in a dose-dependent manner.

Conclusion: We identified two specific epitopes from human native ApoB100 that trigger T-cell activation and protect HuBL mice against atherosclerosis when used in a vaccine. Our data suggest that vaccination-induced protective mechanisms may be mediated at least in part through specific antibody responses to LDL that inhibit macrophage activation.

Keywords: T-cell; apolipoprotein B-100; atherosclerosis; epitopes; vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoprotein B-100 / immunology*
  • Apolipoprotein B-100 / metabolism
  • Atherosclerosis / immunology*
  • Atherosclerosis / prevention & control*
  • Disease Models, Animal
  • Epitopes, T-Lymphocyte / immunology*
  • HLA-D Antigens / metabolism
  • Humans
  • Immunoglobulin G / biosynthesis
  • Inflammation / prevention & control
  • Macrophages / immunology
  • Mice
  • Mice, Transgenic
  • Plaque, Atherosclerotic / immunology
  • Vaccination*


  • Apolipoprotein B-100
  • Epitopes, T-Lymphocyte
  • HLA-D Antigens
  • Immunoglobulin G