| Vaccine description | |
|---|---|
| Target | Hypertension |
| Vaccine type | Conjugate |
| Clinical data | |
| Routes of administration | Subcutaneous |
| ATC code |
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| Legal status | |
| Legal status |
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| Identifiers | |
| ChemSpider |
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CYT006-AngQb was an investigational vaccine against angiotensin II, designed to lower blood pressure. It was somewhat effective in clinical trials, but less so than conventional drugs against hypertension (elevated blood pressure). [1]
Angiotensin II causes blood vessels to constrict, and drives blood pressure up. CYT006-AngQb consists of virus-like particles covalently coupled to angiotensin II. Subcutaneous injection causes the immune system to produce antibodies which reduce angiotensin II blood levels, lowering blood pressure.
In a 2008 phase IIa study, 72 patients received 100 μg, 300 μg or placebo in weeks 0, 4, and 12. Blood pressure was lowered dose-dependently, by 5.6 mmHg (systolic) and 2.8 mmHg (diastolic) in the 300 μg group. Morning blood pressure (5:00-8:00) was lowered by 25 mmHg (systolic) and 13 mmHg (diastolic).
Side effects were mild and included local reactions, headache and fatigue. [2]
The 2008 trial was small and exploratory. It did not address the question of whether the vaccine actually protects internal organs, nor did it address safety concerns such as whether the vaccine would cause autoimmune disease. If a standard drug treatment is found to dangerously inhibit the renin-angiotensin-aldosterone system, it can be withdrawn and the effects reversed quickly, but that would not be true of the vaccine. However, poor compliance to standard treatment is the main reason for inadequate control of blood pressure, and if vaccination were safe and effective in the long run, it may solve many compliance problems. [3]
CYT006-AngQb did not reach Phase III studies because the antihypertensive effects were small compared to existing ACE inhibitors and angiotensin II receptor antagonists, and they were not reproducible across dosing schemes. Similar vaccines with modified immunogens and different adjuvants are being investigated. [1] [4]
Angiotensin-converting-enzyme inhibitors are a class of medication used primarily for the treatment of high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart.
Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" refers to the pressure in a brachial artery, where it is most commonly measured. Blood pressure is usually expressed in terms of the systolic pressure over diastolic pressure in the cardiac cycle. It is measured in millimeters of mercury (mmHg) above the surrounding atmospheric pressure, or in kilopascals (kPa). The difference between the systolic and diastolic pressures is known as pulse pressure, while the average pressure during a cardiac cycle is known as mean arterial pressure.
Hypertension, also known as high blood pressure, is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms itself. It is, however, a major risk factor for stroke, coronary artery disease, heart failure, atrial fibrillation, peripheral arterial disease, vision loss, chronic kidney disease, and dementia. Hypertension is a major cause of premature death worldwide.
The renin–angiotensin system (RAS), or renin–angiotensin–aldosterone system (RAAS), is a hormone system that regulates blood pressure, fluid and electrolyte balance, and systemic vascular resistance.
Pulse pressure is the difference between systolic and diastolic blood pressure. It is measured in millimeters of mercury (mmHg). It represents the force that the heart generates each time it contracts. Healthy pulse pressure is around 40 mmHg. A pulse pressure that is consistently 60 mmHg or greater is likely to be associated with disease, and a pulse pressure of 50 mmHg or more increases the risk of cardiovascular disease. Pulse pressure is considered low if it is less than 25% of the systolic. A very low pulse pressure can be a symptom of disorders such as congestive heart failure.
Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.
Indapamide is a thiazide-like diuretic drug used in the treatment of hypertension, as well as decompensated heart failure. Combination preparations with perindopril are available. The thiazide-like diuretics reduce risk of major cardiovascular events and heart failure in hypertensive patients compared with hydrochlorothiazide with a comparable incidence of adverse events. Both thiazide diuretics and thiazide-like diuretics are effective in reducing risk of stroke. Both drug classes appear to have comparable rates of adverse effects as other antihypertensives such as angiotensin II receptor blockers and dihydropyridine calcium channel blockers and lesser prevalence of side-effects when compared to ACE-inhibitors and non-dihydropyridine calcium channel blockers.
Essential hypertension is a form of hypertension without an identifiable physiologic cause. It is the most common type affecting 85% of those with high blood pressure. The remaining 15% is accounted for by various causes of secondary hypertension. Essential hypertension tends to be familial and is likely to be the consequence of an interaction between environmental and genetic factors. Hypertension can increase the risk of cerebral, cardiac, and renal events.
In medicine, the mean arterial pressure (MAP) is an average calculated blood pressure in an individual during a single cardiac cycle. Although methods of estimating MAP vary, a common calculation is to take one-third of the pulse pressure, and add that amount to the diastolic pressure. A normal MAP is about 90 mmHg.
Candesartan is an angiotensin receptor blocker used mainly for the treatment of high blood pressure and congestive heart failure. Candesartan has a very low maintenance dose. Like Olmesartan, the metabolism of the drug is unusual as it is a cascading prodrug. Candesartan has good bioavailibility and is the most potent by weight of the AT-1 receptor antagonists.
Perindopril is a medication used to treat high blood pressure, heart failure, or stable coronary artery disease.
The Dietary Approaches to Stop Hypertension or the DASH diet is a diet to control hypertension promoted by the U.S.-based National Heart, Lung, and Blood Institute, part of the National Institutes of Health (NIH), an agency of the United States Department of Health and Human Services. The DASH diet is rich in fruits, vegetables, whole grains, and low-fat dairy foods. It includes meat, fish, poultry, nuts, and beans, and is limited in sugar-sweetened foods and beverages, red meat, and added fats. In addition to its effect on blood pressure, it is designed to be a well-balanced approach to eating for the general public. DASH is recommended by the United States Department of Agriculture (USDA) as a healthy eating plan. The DASH diet is one of three healthy diets recommended in the 2015–20 U.S. Dietary Guidelines, which also include the Mediterranean diet and a vegetarian diet. The American Heart Association (AHA) considers the DASH diet "specific and well-documented across age, sex and ethnically diverse groups."
In medicine, systolic hypertension is defined as an elevated systolic blood pressure (SBP). If the systolic blood pressure is elevated (>140) with a normal (<90) diastolic blood pressure (DBP), it is called isolated systolic hypertension. Eighty percent of people with systolic hypertension are over the age of 65 years old. Isolated systolic hypertension is a specific type of widened pulse pressure.
Renin inhibitors are pharmaceutical drugs inhibiting the activity of renin that is responsible for hydrolyzing angiotensinogen to angiotensin I, which in turn reduces the formation of angiotensin II that facilitates blood pressure.
The angiotensin receptor blockers (ARBs), also called angiotensin (AT1) receptor antagonists or sartans, are a group of antihypertensive drugs that act by blocking the effects of the hormone angiotensin II in the body, thereby lowering blood pressure. Their structure is similar to Ang II and they bind to Ang II receptors as inhibitors, e.g., [T24 from Rhys Healthcare].
Renal sympathetic denervation (RSDN) is a minimally invasive, endovascular catheter based procedure using radiofrequency ablation or ultrasound ablation aimed at treating resistant hypertension. Nerves in the wall of the renal artery are ablated by applying radiofrequency pulses or ultrasound to the renal arteries. This causes reduction of sympathetic afferent and efferent activity to the kidney and blood pressure can be decreased. Early data from international clinical trials without sham controls was promising - demonstrating large blood pressure reductions in patients with treatment-resistant hypertension. However, in 2014 a prospective, single-blind, randomized, sham-controlled clinical trial failed to confirm a beneficial effect on blood pressure. A 2014 consensus statement from The Joint UK Societies did not recommend the use of renal denervation for treatment of resistant hypertension on current evidence. More recent sham-controlled trials suggest renal denervation can lead to lower systolic blood pressure.
EMA401 is a drug under development for the treatment of peripheral neuropathic pain. Trials were discontinued in 2015, with new trials scheduled to begin March, 2018. It was initially established as a potential drug option for patients suffering pain caused by postherpetic neuralgia. It may also be useful for treating various types of chronic neuropathic pain EMA401 has shown efficacy in preclinical models of shingles, diabetes, osteoarthritis, HIV and chemotherapy. EMA401 is a competitive antagonist of angiotensin II type 2 receptor (AT2R) being developed by the Australian biotechnology company Spinifex Pharmaceuticals. EMA401 target angiotensin II type 2 receptors, which may have importance for painful sensitisation.
Arterial blood pressure is most commonly measured via a sphygmomanometer, which historically used the height of a column of mercury to reflect the circulating pressure. Blood pressure values are generally reported in millimetres of mercury (mmHg), though aneroid and electronic devices do not contain mercury.
Hypertensive disease of pregnancy, also known as maternal hypertensive disorder, is a group of high blood pressure disorders that include preeclampsia, preeclampsia superimposed on chronic hypertension, gestational hypertension, and chronic hypertension.
Hypertension is a condition characterized by an elevated blood pressure in which the long term consequences include cardiovascular disease, kidney disease, adrenal gland tumors, vision impairment, memory loss, metabolic syndrome, stroke and dementia. It affects nearly 1 in 2 Americans and remains as a contributing cause of death in the United States. There are many genetic and environmental factors involved with the development of hypertension including genetics, diet, and stress.