PMID- 14651724
OWN - NLM
STAT- MEDLINE
DCOM- 20040202
LR  - 20190513
IS  - 0306-5251 (Print)
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Linking)
VI  - 56
IP  - 5
DP  - 2003 Nov
TI  - Evaluation of two carrier protein-angiotensin I conjugate vaccines to assess 
      their future potential to control high blood pressure (hypertension) in man.
PG  - 505-12
AB  - AIMS: 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. CONCLUSION: 
      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.
FAU - Downham, M R
AU  - Downham MR
AD  - Protherics plc. (PMD), The Heath Business & Technical Park, Runcorn, UK. 
      matthew.downham@protherics.com
FAU - Auton, T R
AU  - Auton TR
FAU - Rosul, A
AU  - Rosul A
FAU - Sharp, H L
AU  - Sharp HL
FAU - Sjostrom, L
AU  - Sjostrom L
FAU - Rushton, A
AU  - Rushton A
FAU - Richards, J P
AU  - Richards JP
FAU - Mant, T G K
AU  - Mant TG
FAU - Gardiner, S M
AU  - Gardiner SM
FAU - Bennett, T
AU  - Bennett T
FAU - Glover, J F
AU  - Glover JF
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Carrier Proteins)
RN  - 0 (Immunoglobulins)
RN  - 0 (Tetanus Toxoid)
RN  - 0 (Vaccines, Conjugate)
RN  - 9013-72-3 (Hemocyanins)
RN  - 9041-90-1 (Angiotensin I)
RN  - FV4Y0JO2CX (keyhole-limpet hemocyanin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Angiotensin I/*immunology
MH  - Animals
MH  - Carrier Proteins/*therapeutic use
MH  - Dose-Response Relationship, Immunologic
MH  - Drug Evaluation
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Hemocyanins/*therapeutic use
MH  - Humans
MH  - Hypertension/immunology/*therapy
MH  - Immunization
MH  - Immunoglobulins/immunology
MH  - Immunotherapy/methods
MH  - Male
MH  - Middle Aged
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tetanus Toxoid/*therapeutic use
MH  - Vaccines, Conjugate/therapeutic use
PMC - PMC1884403
EDAT- 2003/12/04 05:00
MHDA- 2004/02/03 05:00
PMCR- 2004/05/01
CRDT- 2003/12/04 05:00
PHST- 2003/12/04 05:00 [pubmed]
PHST- 2004/02/03 05:00 [medline]
PHST- 2003/12/04 05:00 [entrez]
PHST- 2004/05/01 00:00 [pmc-release]
AID - 1926 [pii]
AID - 10.1046/j.1365-2125.2003.01926.x [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2003 Nov;56(5):505-12. doi: 
      10.1046/j.1365-2125.2003.01926.x.