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Taking a Shot at Hypertension

A team of Swiss researchers has designed a vaccine that lowers blood pressure.
March 12, 2008

For people with high blood pressure, maintaining a healthy lifestyle and taking a daily dose of pills is essential to keeping hypertension at bay. Now scientists from the Swiss biotechnology company Cytos have created a vaccine that lowers blood pressure. They say that it may one day eliminate the need for daily medication.

Taking the pressure off: Researchers in Switzerland have designed a new vaccine that lowers blood pressure. The vaccine is made of virus-like particles (blue) covered by small receptors (yellow). These receptors bind to angiotensin II, a key molecule in the body that’s responsible for constricting blood vessels and raising blood pressure.

“Pills have to be taken daily, and more than half of the people don’t take their prescribed drugs,” says Martin Bachmann, Cytos’s chief scientific officer. “A vaccine could solve this issue, since it would likely only have to be injected two to three times a year.”

Most antihypertensive drugs today act on a biological system that regulates blood pressure. The molecule angiotensin II plays a key role in this system, as it stimulates blood vessels to constrict, raising blood pressure. It can also produce a hormone that increases sodium and water retention, which in turn elevates blood pressure. Drugs known as receptor blockers have been designed to inhibit angiotensin II. Other drugs, called ACE inhibitors, altogether prevent the production of angiotensin II.

The new vaccine developed by Cytos also targets angiotensin II, with longer-lasting effects compared with conventional drugs. The vaccine itself is made up of virus-shaped particles covered with small receptors designed to bind with angiotensin II. When released into the bloodstream, these virus particles attract and lock onto the molecule. In response, the immune system, recognizing the virus as a foreign body, launches a defense. Antibodies attack the virus-bound angiotensin II, preventing it from constricting blood vessels and raising blood pressure.

Bachmann and his colleagues recently tested the vaccine on 72 people with mild to moderate forms of hypertension, and the team has published its results in the current issue of Lancet. In their study, the researchers randomly divided volunteers into three groups. One group received small doses of the vaccine, and another received larger doses, while the last received a placebo. The day before researchers administered the vaccine, they gave volunteers a blood-pressure monitor, which recorded readings every 15 minutes over 24 hours, providing a baseline measurement.

Volunteers returned for additional vaccinations one month and three months after the initial injection and reported any side effects via telephone. Two weeks after the last injection, the volunteers once again took home a monitor, which measured blood pressure throughout the day.

The team found that most volunteers tolerated the vaccine relatively well, albeit with minimal side effects, including flu-like symptoms and mild irritation at the site of injection. As for changes in blood-pressure levels, researchers compared monitor readings pre- and post-vaccination, and found that volunteers with a higher dose of the vaccine exhibited lower average blood pressure, with a surprising dip in the early-morning hours. Later in the day and through the night, there was little change among all volunteer groups. Bachmann says that it’s unclear why the vaccine has a stronger effect in the early hours of the day, although he has some ideas.

“We hypothesize that the antibodies function like a sponge, which ‘sucks up’ all the generated angiotensin molecules,” says Bachmann. “Since little angiotensin II is generated during the night, the sponge is ‘empty’ early in the morning, and therefore functions best at this time.”

Bachmann adds that lowering early-morning blood pressure may reduce the risk of heart attack and stroke, which have been known to occur more frequently in the morning, as blood-pressure levels spike. A long-lasting vaccine that accomplishes this goal may offer more comprehensive relief, as opposed to pills taken on a daily basis.

“Due to the short half-life of these classical drugs, they don’t work very well early in the morning, since people usually take their pills around breakfast,” says Bachmann. “However, it is early in the morning when most heart attacks and strokes happen, and our trial demonstrated very good efficacy early in the morning.”

Some scientists, however, raise concerns over a vaccine’s long-lasting and potentially irreversible effects on blood pressure. For example, Michael Alderman, an expert in hypertension and the chairman of the department of epidemiology and social medicine at Albert Einstein College of Medicine, in the Bronx, NY, says that there are daily situations in which raising blood pressure is an advantage.

“If you’re running down a football field or walking up a flight of stairs, blood pressure goes up to prevent you from fainting,” says Alderman. “People who have taken antihypertensive medications have been known to faint, and the same risk exists with pills. But you’re changing the equation if you’re on a longer-term effect that you cannot reverse easily.”

Additionally, it is unclear how the vaccine would affect the immune system as it stimulates antibodies continuously over a period of several months.

Bachmann says that after analyzing blood samples from volunteers after the trial, his group found no change in the amount of antibodies and other immune cells present, indicating that the vaccine had minimal effect on immune-system production.

Cytos plans to find a pharmaceutical partner in the next few months to collaborate on a larger trial of the vaccine, and together they will work on fine-tuning dosage to further lower blood pressure, particularly in people with mild to moderate forms of hypertension.

“We would expect the vaccine to be particularly useful in this patient population, since the vaccine alone may suffice to control blood pressure,” says Bachmann. “In more severely hypertensive patients, this would most likely not be the case, since they usually need more than one type of drug.”

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