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Anti-Atherosclerotic Vaccination with T-Cell Peptides Is Most Effective in Reducing Plaque in the Thoracic Aorta
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Kevin Tse, MD, Takayuki Kimura, MD, Harley Tse, Ph.D., Alessandro Sette, Dr. Biol. Sci., Klaus Ley, M.D., John Sidney
Rationale:

We previously demonstrated T-cell peptides derived from murine ApoB100 can be used to vaccinate against atherosclerosis, possibly via a mechanism akin to allergy immunotherapy.  Here, we studied whether different portions of the aorta responded more readily to vaccination than others.

Methods:

15-mer peptide sequences spanning ApoB100 were synthesized and screened for ability to bind tightly to MHC class II.  Candidate peptides (CP3, CP6, CP101 - CP103) were used to vaccinate female ApoE KO mice using 50 mcg of peptide+CFA subcutaneously in the inguinal area at 8 weeks of age. Western diet was started at 10 wks of age. Repeated boosters with 25 mcg peptide+IFA were administered intraperitoneally at age 12, 16, 20 and 22 weeks.  Mice were sacrificed at age 23 weeks and organs were harvested for analysis.  PBS and irrelevant peptide were used as controls.

Results:

CP3 was 30% protective in the aortic arch, nearly 50% protective in the thoracic aorta (p<0.05), and trended toward significant protection in the abdominal aorta. CP6 was 50% protective in the thoracic aorta (p<0.05).  CP101 - P103 were three additional candidate peptides that were tested which conferred similar degrees of atheroprotection, most notably in the thoracic aorta (50% protection, p<0.05).  

Conclusions:

Vaccination with peptide fragments from murine ApoB100 confer the greatest amount of atheroprotection in the thoracic aorta.  The consequences of these regional differences will need to be elucidated before atheroprotective vaccination can proceed to human trials.