The hypertension vaccine of "one injection without taking medicine" is coming?

Intern/Cao Yuan

"The hypertension vaccine is coming soon, so you don't have to take medicine for an injection!" Recently, the news that the hypertension vaccine will be launched in China in 2022 has circulated on the Internet. "Doctor, when will I get the hypertension vaccine?" Fang Hong, chief physician of the Department of Cardiovascular Medicine of Shanghai Tongji Hospital, will be asked by patients about the hypertension vaccine from time to time, "They all want to get this vaccine, come and consult with me." ”

The news that the hypertension vaccine will be available in 2022 first stemmed from the 6th Central Cardiology Conference held in 2016. At this meeting, Liao Yuhua, director of the Department of Cardiovascular Medicine of Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology, announced that the hypertension vaccine that his team has studied for more than ten years has entered the preclinical stage and is expected to be applied to the clinic as soon as 6 years, that is, in 2022.

In 2012, Liao Yuhua's team published an article saying that the antihypertensive vaccine they developed (ATRQβ-001) showed in animal tests that the vaccine had a significant antihypertensive effect and had a certain protective effect on target organs. If approved, it will be the first hypertension vaccine independently developed in China.

But unlike the hypertension vaccine that will be launched in 2022, Liao Yuhua responded to China News Weekly, "At present, we are in the process of pilot sample development, waiting for the clinical trial stage to introduce this project." It is expected that the vaccine will not be available until 2026. ”

Fang Hong reminded patients not to over-mythologize hypertension vaccines, "At present, hypertension vaccine research is basically in the pre-clinical exploration stage, and many problems have not been solved. "At present, for most patients with hypertension, taking medication for the treatment of hypertension and improving their lifestyle in accordance with their doctor's advice is still a fundamental measure.

A new path for the treatment of hypertension

Cardiovascular disease is one of the main killers that threaten human health, and hypertension is the most common cardiovascular chronic disease. There are 245 million high blood pressure patients in China's adults aged 18 and over, which means that on average one in every 5 to 6 people in the country has hypertension. About 1.28 billion adults aged 30 to 79 worldwide suffer from high blood pressure.

At present, the treatment of hypertension relies mainly on oral antihypertensive drugs. Different drugs have different mechanisms of action, mainly by influencing the system that plays an important role in blood pressure regulation to exert antihypertensive effects, such as sympathetic nervous system, renin-angiotensin-aldosterone system (RAAS), endothelin system, etc. Commonly used antihypertensive drugs include calcium channel blockers (CCB), angiotensin-converting enzyme inhibitors (ACE Inhibitors), angiotensin receptor antagonists (ARBs), diuretics, and β receptor blockers.

Fang Hong, who has long been engaged in basic research on hypertension vaccines, explained that unlike antihypertensive drugs, the principle of action of antihypertensive vaccines is to stimulate the body to produce antibodies that affect related enzymes and receptors, so as to achieve the purpose of controlling blood pressure. In the human body, the renin-angiotensin-aldosterone system (RAAS) plays a very important role in the regulation, maintenance and development of blood pressure. The current hypertension therapeutic vaccine mainly works against RAAS, which induces the body to produce antibodies to block RAAS and achieve the purpose of controlling blood pressure.

According to the 2018 Revised Edition of the Chinese Guidelines for the Prevention and Treatment of Hypertension, the awareness rate of hypertension in people over 18 years old in China is about 51.6%, the treatment rate is 45.8%, and the control rate is only 16.8%. Globally, about 720 million people with hypertension do not receive the necessary treatment, and less than a quarter of women and less than one in five men effectively control their blood pressure at normal levels.

Poor treatment adherence in hypertensive patients is one of the key factors in poor blood pressure control. At present, the treatment of hypertension mainly relies on oral antihypertensive drugs. To achieve target blood pressure levels, most patients with hypertension require two or more antihypertensive drugs, and antihypertensive drugs need to be taken once or even multiple times a day. However, due to the asymptomatic and chronic features of hypertension in the early stages, patients have poor drug adherence and poor blood pressure control.

Therefore, the main purpose of the research and development of hypertension vaccines is to improve patient compliance by reducing the number of medications, so as to achieve the purpose of controlling blood pressure. Fang Hong told China News Weekly that different antihypertensive vaccines are injected once every 1 to 3 months, and their efficacy lasts longer than antihypertensive drugs. This means that patients with hypertension only need to be vaccinated with antihypertensive vaccine every 1 to 3 months in the future, without daily medication, the frequency of medication is reduced, and the treatment effect is prolonged, which will effectively improve the compliance and control rate of hypertension treatment.

Related studies have shown that antihypertensive vaccines can not only lower blood pressure, but also have a certain protective effect on target organs, including preventing damage to the kidneys, heart, brain and arteries. Hypertension is a cardiovascular syndrome that is often associated with other cardiovascular risk factors, target organ damage, and clinical disorders. The use of antihypertensive vaccines can also control the toxic side effects of long-term use of antihypertensive drugs. In addition, antihypertensive vaccines can also avoid the adverse reactions and side effects of drug therapy.

Internationally, therapeutic vaccines for hypertension mainly target RAAS, and the main substances in the RAAS system include renin, angiotensin I (Ang I), angiotensin II (Ang II) and AT1R. Therefore, according to the corresponding mechanism of action of the vaccine, hypertension vaccine is also divided into renin vaccine, Ang I vaccine, Ang II vaccine, AND1R vaccine.

The earliest antihypertensive vaccine that humans tried was the renin vaccine. But because such vaccines can cause autoimmune damage to the kidneys, researchers are turning to other targets. Subsequently, a hypertension vaccine targeting AngI was successfully developed. Represented by the PMD series of drugs developed by BTG International Limited, including PMD2850 and PMD3117. In addition, Ang II is also the main target of many hypertension vaccines, including the CYT006-AngQb vaccine developed by the Swiss company Cytos in 2007, and the angiotensin II-DNA vaccine developed by Japanese scholars in 2015.

In China, Liao Yuhua's team focused on the vaccine target on AT1R, first developed the antihypertensive vaccine ATR12181, and on this basis, developed the ATRQβ-001 vaccine. Animal experiments have shown that the vaccine can significantly reduce blood pressure and effectively inhibit myocardial fibrosis, and in the later stages of vaccination, the vaccine group is very similar to the antihypertensive range of valsartan. On June 17, 2021, the "ATRQβ-001 Therapeutic Antihypertensive Vaccine" project received strategic investment from Saili Medical.

"Due to the different conditions and conditions of different experiments, it is not possible to directly compare which type of antihypertensive vaccine has a better effect." However, Fang Hong's preliminary judgment said, "The vaccine acting on angiotensin II. has the strongest antihypertensive effect, while the vaccine effect affecting the AT1R receptor is relatively weak." ”

Don't over-mythologize antihypertensive vaccines

Fang Hong reminded, "The hypertension vaccine is not as magical as imagined! "This is because the vaccine is a therapeutic vaccine that is applied to people who already have high blood pressure and does not prevent high blood pressure." Liao Yuhua also stressed in 2019 that it is not necessary to confuse therapeutic vaccines with preventive vaccines. The former acts on patients who have already developed the disease, with the purpose of treating the disease, while the latter is applied to healthy people in order to prevent the disease.

The hypertension vaccine is not what the Internet rumors say, and has the effect of "one shot cure". Antibody titers affect the protective effect of vaccines, and antibody titers generally decay over time, and antihypertensive vaccines are expected to take 1 to 3 months to strengthen immunity once, and cannot be "one shot forever". Liao Yuhua's team's animal tests also showed that the antihypertensive effect of the experimental group gradually decreased with the titer of the vaccine antibody, and it was also gradually weakened compared with the control group using drugs.

In addition, Fang Hong also said that because the pathogenesis of hypertension is complex and diverse, not all hypertension is caused by the RASS system. But the hypertension vaccine targets only a single target of RASS, so the hypertension vaccine does not prevent the development of hypertension or treat all types of hypertension.

Zhou Zihua, chief physician of the Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology, also pointed out in the paper that patients with severe hypertension have high blood pressure, the pathogenesis is more complex, and the benefits of hypertension vaccination are limited. In addition, patients with hypertension who have immunodeficiency or autoimmune diseases and those who are allergic to hypertensive vaccines are not suitable for hypertension vaccination.

"At present, oral antihypertensive drugs are still the most mature and effective way to treat high blood pressure." But Fang Hong pointed out. At present, some hypertensive patients have the wrong psychology of "not willing to take medicine", "thinking that after eating high blood pressure drugs, they cannot get rid of it for a lifetime, and they are addicted like drugs." He stressed that patients need to understand the causal relationship, not because they can't stop taking antihypertensive drugs, but because there is no way to cure hypertension at present, and they must rely on drugs to control blood pressure.

Risk factors for hypertension include genetic factors, age, and a variety of poor lifestyles. Fang Hong stressed that while adhering to drug treatment, we should also fundamentally change bad living habits and establish a healthy lifestyle.