An Antibody Approach To Preventing Sepsis

Research in mice suggests that a new antibody-based therapy could be a valuable weapon in the battle against sepsis.

AsianScientist (Apr. 22, 2016) – Researchers in South Korea have succeeded at strengthening blood vessels against the effects of sepsis, or blood poisoning, an often-fatal infection. Their findings have been published in Science Translational Medicine.

Sepsis is a serious healthcare problem that is more common than heart attacks and kills more people than any type of cancer. Despite this substantial burden, it remains poorly understood.

Sepsis is caused by the immune system severely overreacting to an infection and attacking itself. The first thing that occurs is the weakening of blood vessels, which makes them porous and causes vascular leakage leading to a cascade of compounding negative effects, including severe inflammation, organ damage, pulmonary edema and death.

Currently, doctors are only able to treat sepsis symptomatically by fighting the underlying infection and hoping that the body gets strong enough to combat the sepsis on its own. However, researchers at the Institute for Basic Science’s (IBS) Center for Vascular Health have now developed an antibody-based therapy for mitigating sepsis by strengthening, as well as protecting, blood vessels.

The research team’s method for alleviating sepsis progression focuses on activating a receptor in the lining of blood vessels called endothelial cells. They induced a protein growth factor called TIE2, which stimulates blood vessel growth by using an anti-angiopoietin-2 (Ang2) antibody called ABTAA (Ang2-binding and TIE2-activating antibody).

Under normal conditions, Ang2 is barely detectable in the body. But during times of high stress, like a severe infection, it is created en masse and circulates through the bloodstream, causing vascular cell death and making the blood vessels porous. ABTAA works by simultaneously causing Ang2 inhibition and TIE2 activation.

ABTAA prevents this by causing Ang2 to clump together, rendering it inert and unable to cause damage, while also stimulating TIE2, which strengthens blood vessels. Encouragingly, the combination of ABTAA and antibiotics enhanced the survival rates of severe sepsis models up to 70 percent.

Even more intriguing is the possibility for ABTAA to be used as part of a cure for life-threatening infections such as the Ebola or MERS viruses, since both are known to cause devastating disintegration of vascular systems, the authors say.


The article can be found at: Han et al. (2016) Amelioration of Sepsis by TIE2 Activation-Induced Vascular Protection.

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Source: Institute for Basic Science.
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