Vaccine Induces Protective Immune Response in Mouse Model

Vaccination of mice with a peptide derived from the apoB protein component of low density lipoprotein (LDL) stimulated increased production of regulatory T-cells (Tregs) and reduction in number and size of atherosclerotic lesions.

Immunization with apolipoprotein B (apoB, core protein of low density lipoprotein) is known to be atheroprotective in animal models. While CD4+ T-cells play an important role in atherosclerosis, their antigen specificity is poorly understood.

Investigators at the La Jolla Institute for Allergy and Immunology (CA, USA) examined the role of regulatory T-cells during the process of generating an immune response to the apoB peptide p18. For this study the investigators constructed p18-tetramers to detect human and mouse apoB-specific T- cells and assayed their phenotype by flow cytometry including CD4 lineage transcription factors, intracellular cytokines, and TCR (T-cell receptor) activation. Apoe-/- mice were vaccinated with p18 peptide or adjuvants alone and atherosclerotic burden in the aorta was determined.

Results published in the March 27, 2018, online edition of the journal Circulation revealed that apoB p18 specific CD4+ T-cells were mainly Tregs in healthy donors, but co-expressed other CD4 lineage transcription factors in donors with subclinical cardiovascular disease. In Apoe-/- mice, immunization with p18 induced Tregs and reduced atherosclerotic lesions.

"We knew atherosclerosis had an inflammatory component but until recently did not have a way to counteract that," said senior author Dr. Klaus Ley, professor of inflammation biology at the La Jolla Institute for Allergy and Immunology. "We now find that our vaccination actually decreases plaque burden by expanding a class of protective T-cells that curb inflammation."

"We are now engineering vaccines to be more specific," said Dr. Ley. "Once we can manipulate the immune response with a single peptide or epitope, we will be able to create more highly targeted vaccines with fewer non-specific responses."

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La Jolla Institute for Allergy and Immunology