A Vaccine to Prevent Atherosclerosis
- Heart disease is the leading cause of death in the United States.
- Human trials for an atherosclerosis vaccine are underway.
- If successful, this groundbreaking research could be a game-changer for cardiovascular diseases.
Heart disease is the No. 1 cause of death for men and women in the United States.
If you’re among the 82 million people in the United States with atherosclerosis, you’re at risk of a heart attack and stroke.
But what if we had a vaccine to help lower that risk?
“It would be a game-changer for cardiovascular diseases,” P.K. Shah, MD, MACC, told Healthline.
Shah is the Shapell and Webb Endowed Chair in Clinical Cardiology and director of the Oppenheimer Atherosclerosis Research Center and Atherosclerosis Prevention and Treatment Center at the Smidt Heart Institute at Cedars-Sinai in Los Angeles. He’s also a professor of medicine at UCLA and Cedars-Sinai Medical Center.
Dr. Shah and the colleagues in his laboratory at Cedars-Sinai are the main beneficiaries of The Heart Foundation, a nonprofit organization dedicated to saving lives from heart disease through awareness, education, and research. The foundation was formed by friends of Steven Cohen, who died of a massive heart attack at 35 years old.
What is atherosclerosis?
Atherosclerosis, known as “hardening of the arteries,” is a disease that involves plaque buildup and inflammation inside the artery walls. The plaque is composed of low-density lipoprotein (LDL) cholesterol, and it causes the arteries to harden and narrow.
Narrowed arteries make it harder for blood to flow freely to the heart, depriving it of oxygen. It also leads to inflammation. This can cause the plaque to burst and form a clot, cutting off the blood supply. Life threatening events, such as heart attack or stroke, can occur.
“Inflammation results from, in large part, activation of the body’s immune system,” Shah said. “This gave us the idea that taming the immune system might favorably alter the development of plaque and plaque inflammation, thereby reducing the risk of a heart attack or stroke.”
First steps toward a vaccine
The idea to test experimental models occurred in the early 1990s. Shah collaborated with Dr. Jan Nilsson of Sweden, a visiting scientist in Shah’s laboratory at Cedars-Sinai.
“We were able to show, through animal research, that using LDL as an antigen, immunization led to a significant reduction in plaque buildup,” Shah explained. “It seemed to be too good to be true, but repeat experiments again showed the same results. Also, a team of scientists at UC San Diego, who were thinking along similar lines, achieved similar results.”
That led to the idea that modulating the immune system could reduce atherosclerosis, vascular inflammation, and eventually heart attacks and strokes, Shah added.
There are two main components to the vaccine program:
- an active vaccine that involves immunization with an LDL cholesterol-related antigen
- a passive vaccine that involves administration of synthetic monoclonal antibodies against LDL-related antigens
The goal is to generate an immune response to slow atherosclerosis.
“Over the past 20 years, we made a lot of progress in identifying the antigens within the LDL particle and using synthetic peptide mimics of LDL-related antigens. Vaccination with the peptide antigens reproduced results similar to immunization with the whole LDL particle,” Shah said.
An antigen is toxin or other substance in the body that can trigger an immune response.
Ongoing human trials
“The phase 2 human trial of this passive vaccine is ongoing through ABCENTRA, a start-up biotech company,” said Shah.
“Results are expected in a year’s time. If the trials prove successful, potential applications of the passive vaccine or monoclonal antibody (called orticumab) would be in high risk patients with atherosclerosis where short-term treatment could stabilize arterial plaque and reduce inflammation,” he said.
The randomized, double-blind study will compare orticumab with placebo in 75 adults with psoriasis who are at least 30 years old. Treatments will take place at 17 clinical trial centers across the United States.
This trial is currently testing the effects of the monoclonal antibody, orticumab, against an LDL-related antigen called p45 in atherosclerosis in patients with psoriasis.
“The reason for choosing psoriasis patients is that psoriasis is a chronic inflammatory disease with enhanced risk of atherosclerosis development, and in a prior human study, [individuals] receiving this antibody, orticumab, had amelioration of psoriatic skin lesions. Current thinking is that oxidized form of LDL plays a role in psoriasis skin lesions as well as atherosclerosis,” Shah added.
People with psoriasis are up to 50 percent more likely to develop cardiovascular disease.
Should phase 2 trials show a reduction in plaque and/or inflammation, the research can proceed to phase 3 human trials.
Shah said the next step is to show that this passive vaccine reduces the risk of heart attack and stroke in patients with or without psoriasis.
“The passive vaccine is a short-term treatment and would be applicable to patients with known coronary plaque and a high risk for a heart attack,” said Shah.
As for the active vaccine, Shah and his colleagues, including close collaborator, Dr. Kuang-Yuh Chyu, have been testing various formulations of another LDL-related antigen called p210. They’ve found it effective in animal research. But the formulation must be optimized before considering human trials.
“Eventually, if all goes well, this active vaccine could be given to at-risk patients to prevent development of atherosclerosis in order to reduce the risk of heart attack or stroke. A lot more work is needed to define the type of [person] who would most benefit with long-term results,” said Shah.