Active immunization with angiotensin I peptide analogue vaccines selectively reduces the pressor effects of exogenous angiotensin I in conscious rats

Gardiner, Sheila M.; Auton, T. R.; Downham, M R; Sharp, Harvey L.; Kemp, P.A.; March, J E; Martin, Harry; Morgan, Peter J.; Rushton, Alan R.; Bennett, T.; Glover, James F.

doi:10.1038/sj.bjp.0703178

Cited by 49 publications

(34 citation statements)

References 9 publications

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“…With the conjugation of a carrier protein, angiotensin I was shown to be antigenic and safe in animals and humans. 27 However, neither BP nor aldosterone concentration in blood secretion was significantly modifed by angiotensin I immunization in humans. 28 The Ang II vaccine CYT-006-AngQb is a promising therapeutic vaccine based on VLP carrier.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness and Safety of a Therapeutic Vaccine Against Angiotensin II Receptor Type 1 in Hypertensive Animals

et al. 2013

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H ypertension has become a leading disease in both developed (333 million) and undeveloped (639 million) countries. 1 The prevalence of hypertension is expected to increase to 29.2% in 2025 (29% of men and 29.5% of women).1 It is a complex disease caused by multiple factors, 1 of which is the renin-angiotensin system (RAS), which plays a critical role in the development and maintenance of blood pressure. Chemical drugs targeting RAS, including renin inhibitor, angiotensin convert enzyme inhibitor, and angiotensin II (Ang II) receptor blocker (ARB), have exhibited excellent therapeutic effects in clinical practice. Nevertheless, the control rate of blood pressure is still far from being satisfactory worldwide, and the treatment compliance is quite low. 1To address the compliance issue and improve therapeutic outcomes for patients, it is necessary to develop novel methods for hypertension treatment. Vaccines can elicit specific antibodies against hypertension related target molecules, providing a possible avenue toward accomplishing this goal. 2-4One potential target is the Ang II type 1 receptor (AT 1 R), a G protein coupling receptor, which has a second extracellular loop (ECL2) that plays an important role in activation of the receptor. 5 The 181 Ala and 183 His residues in the ECL2 are 2 possible binding sites of Ang II with AT 1 R. 5,6 In our previous work, we demonstrated that an epitope from the rat AT 1 R, designated as ATR12181, can decrease the systolic blood pressure (SBP) of spontaneously hypertensive rats (SHRs) and provide excellent protective effects in target organs. 7Following our work, another study team emphasized vaccination against AT 1 R for the prevention of l-NAME-induced nephropathy. 8 Here, a linear epitope ATR-001, derived from the ECL2 of human AT 1 R including 181 Ala and 183 His, was designed. To improve the low immunogenicity of ATR-001, it was conjugated with a virus-like particle (VLP) carrier protein, whose remarkable feature is the highly repetitive and ordered surface structure and have been used in the treatment of several chronic diseases. 9,10Abstract-Primary hypertension is a chronic disease with high morbidity, and the rate of controlled blood pressure is far from satisfactory, worldwide. Vaccination provides a promising approach for treatment of hypertension and improvement in compliance. Here, the ATRQβ-001 vaccine, a peptide (ATR-001) derived from human angiotensin II (Ang II)

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Section: Discussionmentioning

confidence: 99%

Effectiveness and Safety of a Therapeutic Vaccine Against Angiotensin II Receptor Type 1 in Hypertensive Animals

et al. 2013

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“…Angiotensin II directly stimulates the transforming growth factor ␤ pathway in kidney (28,29), and is known to modulate tubulointerstitial fibrosis in animal models of chronic kidney disease (30). Interestingly, circulating levels of angiotensin II have been shown to be significantly higher in hemodialysis patients with hypotension compared with those with normal blood pressure (31), whereas others could not find a difference in angiotensin II levels between control subjects and diabetics with or without nephropathy (32).…”

Section: Discussionmentioning

confidence: 91%

Protein Microarrays Discover Angiotensinogen and PRKRIP1 as Novel Targets for Autoantibodies in Chronic Renal Disease

Butte

Sigdel

Wadia

et al. 2011

Molecular & Cellular Proteomics

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Biomarkers for early detection of chronic kidney disease are needed, as millions of patients suffer from chronic diseases predisposing them to kidney failure. Protein microarrays may also hold utility in the discovery of autoantibodies in other conditions not commonly considered auto-immune diseases. We hypothesized that proteins are released as a consequence of damage at a cellular level during end-organ damage from renal injury, not otherwise recognized as self-antigens, and an adaptive humoral immune response to these proteins might be detected in the blood, as a noninvasive tracker of this injury. The resultant antibodies (Ab) detected in the blood would serve as effective biomarkers for occult renal injury, enabling earlier clinical detection of chronic kidney disease than currently possible, because of the redundancy of the serum creatinine as a biomarker for early kidney injury. To screen for novel autoantibodies in chronic kidney disease, 24 protein microarrays were used to compare serum Ab from patients with chronic kidney disease against matched controls. From a panel of 38 antigens with increased Ab binding, four were validated in 71 individuals, with (n ‫؍‬ 50) and without (n ‫؍‬ 21) renal insufficiency. Significant elevations in the titer of novel auto-Ab were noted against angiotensinogen and PRKRIP1 in renal insufficiency. Current validation is underway to evaluate if these auto-Ab can provide means to follow the evolution of chronic kidney disease in patients with early stages of renal insufficiency, and if these rising titers of these auto-Ab correlate with the rate

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“…Vaccinated rats had blunted responses to exogenous angiotensin I on day 63 and had no response to angiotensin II administration. The anti-angiotensin antibody titer increased 32, 100 fold [10].…”

Section: Angiotensin I Vaccinementioning

confidence: 99%

Blood Pressure Vaccines

Phisitkul¹,

Topf

2014

Chronic Kidney Disease and Hypertension

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Active immunization with angiotensin I peptide analogue vaccines selectively reduces the pressor effects of exogenous angiotensin I in conscious rats

Cited by 49 publications

References 9 publications

Effectiveness and Safety of a Therapeutic Vaccine Against Angiotensin II Receptor Type 1 in Hypertensive Animals

Effectiveness and Safety of a Therapeutic Vaccine Against Angiotensin II Receptor Type 1 in Hypertensive Animals

Protein Microarrays Discover Angiotensinogen and PRKRIP1 as Novel Targets for Autoantibodies in Chronic Renal Disease

Blood Pressure Vaccines

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