Novel vaccine could work as well as clopidogrel to prevent ischemic stroke
A therapeutic vaccine developed in Japan could work as well as oral antithrombotic drugs to prevent secondary ischemic stroke, according to preliminary research published Oct. 29 in Hypertension.
Study author Hironori Nakagami, MD, PhD, of Osaka University and colleagues said while stroke is a major complication of hypertension and is often related to thrombosis, long-term treatment and prevention isn’t a priority for heart patients. Up to 30 percent of strokes are recurrent, but studies have found anywhere between 22 and 36 percent of repeat stroke patients discontinue their antiplatelet therapy within months of an infarction.
Since a range of factors affect a patient’s adherence to a drug regimen—including socioeconomic status, psychological disorders and medical history—Nakagami et al. focused on a non-oral prevention agent.
“Decreased adherence to daily ingestion of antiplatelet drugs is a critical issue, increasing mortality and morbidity in poststroke patients,” the authors wrote. “As vaccination could be a promising approach to solving this, we designed an antiplatelet vaccine that inhibited S100A9/CD36 signaling in platelets, which was reported to be a key signal in arterial thrombosis but not hemostasis.”
S100A9 impedes clot formation by inhibiting the S100 calcium-binding protein, also known as myeloid-related protein-14. Nakagami’s team tested the initial vaccine in mice.
The researchers found immunization with S100A9 induced a sustainable increase in the anti-S100A9 antibody titer in mice for at least two months, with the addition of a booster immunization enhancing that antibody production even further. Middle cerebral artery occlusion time was also prolonged in vaccinated mice—a response comparable to that of treatment with clopidogrel.
The antithrombotic effects of S100A9 lasted on average 84 days after the last vaccination, the authors said. Importantly, the vaccine didn’t seem to trigger any kind of autoimmune response from the mice or increase their risk for hemorrhage.
“Our findings present the possibilities of a safe vaccine-based strategy to prevent recurrent strokes in poorly adherent patients,” Nakagami et al. said. “As S100A9/CD36 signals are related to atherosclerosis, further studies on atherosclerosis may provide additional distinct advantages of this vaccine compared with current antiplatelet agents. An antithrombotic S100A9 vaccine may be a better long-acting treatment than current oral drug medications for the prevention of recurrent ischemic stroke.”