The vaccine – developed by the University of Tokyo to study hypertension in mice – targets the hormone angiotension II (Ang II), a key factor in high blood pressure. It was injected into a group of 53 male rats three times, at four, six and seven weeks old, while a second group were administered saline at the same intervals; ischemic (clot-caused) stroke was induced in both groups.
Vaccinated rats displayed higher levels of anti-Ang II antibodies in functional tissue on the side of the brain where the stroke occurred. Researchers also noted that this group had less damage to the brain and fewer degenerated neurons.
“Cerebral infarct volume was reduced in rats with a sufficient high titer of serum; in particular, more than 6,000,” said the University of Tokyo’s Dr Koji Wakayama. “The infarct size of the high-titer group was less than one-sixth compared to the low-titer group.”
“Reduced neurodegeneration (FJB positive neuron) and oxidative stress (4HNE positive cell) were demonstrated 24 hours after MCAo (artificial stroke induction) in high-titer serum rats.”
Chemically synthesised by Peptide Institute Inc, no previous cell lines or bioreactor were involved in the vaccine’s manufacture, which was solely for animal experimentation.
Dr Wakayama confirmed plans to proceed to human trials. “Our collaborators are now trying to make a GMP-level product and plan to examine the effects using an alternative adjuvant in hypertensive patients,” he said. “If effectiveness is proven in lowering blood pressure in their studies, the vaccine will be tested in stroke patients.” Freund’s adjuvant, banned in human trials, was used to stimulate immune response in the rats.
In addition to protecting the brain after ischemic stroke, it is hoped the Ang II peptide vaccine - which is long-lasting and shows anti-inflammatory properties - may reduce the risk of stroke overall.
“Considering that our collaborator reported the lowered blood pressure in Ang-II-induced hypertensive mice, and hypertension is a major risk of the recurrence of ischemic stroke, we speculate that this vaccine will be a good candidate in secondary prevention in post-stroke hypertensive patients,” said Dr Wakayama.
No drug companies are currently involved in development.