A new vaccine for high blood pressure has sparked a debate on the long-term safety of the approach.

Vaccines for hypertension would solve one of the most vexing problems facing doctors: individuals who don't take their drugs properly. Promising candidates periodically emerge but remain dogged by concerns about unintended immune responses.

In the latest venture, Swiss company Cytos Biotechnology is proposing a vaccine that targets the renin-angiotensin system, which is key to the regulation of blood pressure. The researchers reported at a conference in November that a peptide vaccine derived from angiotensin II, the hormone that causes arteries and veins to constrict, produces an antibody response in humans. In earlier rat studies, the same response translated to a drop in blood pressure, the researchers say.

High blood pressure is a pervasive problem, affecting one in three Americans and nearly 1 billion people worldwide. There is a growing list of effective drugs, including those that block angiotensin's effects, diuretics and calcium-channel blockers. Still, hypertension remains a problem, in part because many of those affected do not take the daily drugs regularly.

A vaccine that is given only a few times a year might solve that problem, says Martin Bachmann, chief scientific officer at Cytos. The Cytos vaccine uses a noninfectious virus-like particle to carry the immunogen. The company is also testing this carrier in clinical trials for vaccines against Alzheimer disease, obesity, nicotine addiction and allergies.

Experts say the company's data are promising but preliminary. Scientists have experimented with vaccines against the renin-angiotensin system for more than 50 years, notes Jean-Baptiste Michel, director of hematology at the Xavier Bichat Hospital in Paris.

Last year, researchers at Cambridge University and UK-based Protherics tested a high blood pressure vaccine that targeted angiotensin I, a precursor to the more powerful angiotensin II. The approach generated antibodies but did not significantly modify blood pressure, Michel says.

Merely generating antibodies does not guarantee that those antibodies can bind and inhibit angiotensin II in tissues—a necessary but risky step, he says. In the early 1990s, Michel himself developed a renin vaccine that blocked the generation of angiotensin in both plasma and tissues. The vaccine induced antibodies in marmosets and reduced the animals' blood pressure. But both primates and rats developed autoimmune disease. Based on his data, Michel says it may not be possible to block angiotensin without targeting it in tissues, which he predicts would inevitably trigger an autoimmune reaction.

Others say a sustained immune response might also have other long-ranging effects.

“High blood pressure is a long-term issue,” says Walinjom Muna, chief of cardiology at the University of Yaoundé in Cameroon. “What are the long-term consequences of permanent receptor blockade in humans or closely related species?”

The Cytos studies do not yet have data to respond to those concerns, says Bachmann, but a phase 1 study showed that antibody levels dropped close to background levels within a few months. There have also been no signs of kidney disease or elevated levels of immune complexes, he adds.