Evaluation of two carrier protein-angiotensin I conjugate vaccines to assess their future potential to control high blood pressure (hypertension) in man.
OBJECTIVE
We aim to modulate the renin-angiotensin system (RAS) by active immunization against angiotensin I hormone (AI), potentially providing a novel conjugate vaccine treatment for hypertension in man.


METHODS
Immunization studies in rat and human subjects compare the effectiveness of tetanus toxoid (TT) and keyhole limpet haemocyanin (KLH) vaccines for immunotherapy following conjugation with an AI peptide analogue (AI). Cardiovascular responses were assessed in immunized rats and human subjects (two-dose trial only), following increasing i.v. infusions of either AI or angiotensin II hormone (AII).


RESULTS
The AI-TT and AI-KLH conjugate vaccines induced an equivalent immune response, and inhibition of the pressor effects to exogenous AI in rats. Single-dose clinical trials with both conjugate vaccines only resulted in an immune response to the KLH carrier protein. A two-dose clinical trial of AI-KLH conjugate vaccine resulted in a significant immune response to AI. A shift in diastolic blood pressure (DBP) dose-response was demonstrated following challenge with AI and AII for the study volunteer showing the largest anti-AI IgG induction.


CONCLUSIONS
KLH was shown to be a suitable alternative to TT as a carrier protein for AI, thus supporting continued evaluation of our AI-KLH conjugate vaccine for treatment of hypertension in man.
Downham
M R
MR
Protherics plc. (PMD), The Heath Business & Technical Park, Runcorn, UK. matthew.downham@protherics.com
Auton
T R
TR
Rosul
A
A
Sharp
H L
HL
Sjöström
L
L
Rushton
A
A
Richards
J P
JP
Mant
T G K
TG
Gardiner
S M
SM
Bennett
T
T
Glover
J F
JF
D000293:Adolescent; D000328:Adult; D000803:Angiotensin I / Q000276:immunology*; D000818:Animals; D002352:Carrier Proteins / Q000627:therapeutic use*; D004306:Dose-Response Relationship, Immunologic; D004341:Drug Evaluation; D004797:Enzyme-Linked Immunosorbent Assay; D006433:Hemocyanins / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000276:immunology / Q000628:therapy*; D007114:Immunization; D007136:Immunoglobulins / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D013745:Tetanus Toxoid / Q000627:therapeutic use*; D018074:Vaccines, Conjugate / Q000627:therapeutic use
D002352:Carrier Proteins; D007136:Immunoglobulins; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; D006433:Hemocyanins; D000803:Angiotensin I; C032808:keyhole-limpet hemocyanin