Vaccine Being Developed for Heart Disease Close to Reality

In his latest finding, Dr. Ley used two mouse peptides, identified by Harley Tse, PhD, from Wayne State University (Detroit, MI, USA), which he integrated into testing the vaccine approach. In the study, vaccinated mice had about 40% less arterial plaque than mice that did not receive the vaccine.

“Heart disease remains our nation's number one killer,” said Mitchell Kronenberg, PhD, La Jolla Institute president and chief scientific officer. “We are excited by Dr. Ley’s studies, which show promise for creating a vaccine that may one day reduce the incidence of this terrible illness.”

The vaccine, if effective, could be administered in an attempt to prevent heart disease, and furthermore, to stop or reduce disease progression. In addition to heart disease, the vaccine could target strokes, which are also fueled by plaque buildup in the arteries. The research elicited excitement from several cardiology experts. Stanley Hazen, MD, PhD, section head of preventive cardiology at the Cleveland Clinic (OH, USA), one of the United States’ top cardiology hospitals, called the research “elegant and tremendously exciting. This lays the groundwork for someday being able to prevent or even eradicate heart disease by giving a vaccine. Truly a remarkably important advance,” said Dr. Hazen, also chairman of the department of cellular and molecular medicine.

Inflammation is also a very important contributor to arterial plaque buildup. “Many research studies over the last 15 years have demonstrated inflammation's critical role in heart disease,” said Dr. Ley. “By creating a vaccine to reduce inflammation in the arteries, we hope to significantly lessen the accompanying plaque buildup.”

Dr. Ley’s study was published December 27, 2014, in the journal Frontiers in Immunology. According to Dr. Ley, the vaccine type he is exploring is different than those people get for the flu and other infections. “A flu vaccine’s purpose is to teach your immune system to launch an attack if it encounters the virus,” he notes. “Our vaccine works more like the desensitization process used in allergy shots. Allergy shots are designed to teach the individual’s immune system to tolerate the allergen. Our vaccine would work on the same principle—only in this case we'd be teaching the immune system to tolerate certain molecules of our own bodies that it mistakenly attacks, which causes inflammation.”

In earlier research, Dr. Ley identified that a specific type of immune cells (CD4 T cells) control the inflammatory attack on the artery wall by receiving antigen-specific signals from other inflammatory cells in the vessel wall. Further, he discovered that these immune cells behave as if they have previously seen the antigen that causes them to launch the attack.

The discovery was particularly exciting since it meant the immune cells had ‘memory’ of the molecule brought forth by the antigen-presenting cells. “Immune memory is the underlying basis of successful vaccines,” Dr. Ley explained. “This meant that conceptually it was possible to consider the development of a vaccine for heart disease.”

Dr. Ley collaborated with fellow La Jolla Institute scientist Alessandro Sette, PhD and Dr. Tse of Wayne State University, to identify the specific peptides, which activate the arterial attack in mice—the byproduct of which is inflammation. The mouse peptides were used in the test vaccine to teach the body, through gradual exposure, to tolerate rather than attack those proteins.

In similar research, Dr. Ley has worked with Dr. Sette, who is an internationally recognized vaccine biologist, to identify more candidate peptides with the objective of ultimately creating a heart disease vaccine for people. “The next step is to test promising candidate peptides in specially engineered mice with an immune system more similar to humans,” he said. If successful, the vaccine could begin human clinical trials in as little as three years, he added.

Related Links:
La Jolla Institute for Allergy and Immunology
Wayne State University