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Saya Otonashi, the central character, is a seemingly ordinary teenage girl adopted and living with amnesia. As her memories return, her life is turned upside down. She was born in 1833, survives on the blood of others, and is destined to destroy chiropterans and her twin sister Diva. Aiding her in her quest are her adopted brothers Kai and Riku and her ever-faithful chevalier Hagi. She also is aided by David, her protector from the powerful organization Red Shield.Diva also has her own helpers, starting with her five powerful chevaliers: Amshel, Solomon, Karl, James and Nathan. They also have their own human allies as part of the Cinq Flèches Group that they operate, including Van Argiano who helps them develop the Delta 67 substance that Cinq Flèches uses to create chiropteran.Working against both sides are the Schiff, a group of escaped artificial chiropteran created by Diva's group. The Schiff attack both groups, believing that the blood of Saya, Diva, or one of their chevaliers will save them from a fatal and painful disease they call the Thorn.

Chiropterans

Chiropterans are hematophagous bat-like creatures that live by feeding on human blood, and generally possess extraordinary speed, strength, and supernatural healing abilities. Some are capable of transforming some of their body parts and of flight. Some higher chiropterans are shown to have the ability to disguise themselves as humans. Chiropterans have a high healing factor, making them difficult, though not impossible to kill. Throughout the series, they are shown surviving heavy gunfire, long falls, being buried under buildings, and explosions. Chiropterans are created from the blood of one of the two queens, with the blood of one queen being deadly to the blood of the chiropterans made from the other queen's blood. Introduction of another queen's blood into a chiropteran's bloodstream begets a deadly chain-reaction, wherein the chriopteran's blood solidifies ("cystalizes"). They are also shown to die through beheading.

The artificial chiropterans created by the Cinq Flèches Group's Delta 67 compound initially are the lowest level form of chiropteran, living and acting purely on instinct. As the series progresses, Dr. Boris and Amshel create the Schiff, a higher form of artificial chiropteran that are sentient, intelligent, and capable of feeling emotions. Unlike all other forms of chiropteran, the Schiff are sensitive to sunlight, and will die if they are directly exposed to it for too long. They also suffer from an unexplained condition which they refer to as "Thorn." This disease slowly crystallizes their blood, eventually resulting in a painful death. Using the genetic template of Moses, the leader of the Schiff, as a template, Cinq Flèches creates what they consider an improved version of the Schiff which they call the Corpse Corps. Similar to their predecessors, the Corpse Corps are capable fighters, but they are depicted as being completely obedient to their creators, and lacking the emotions of the Schiff. They do not appear to suffer from the same issues with sunlight and the Thorn.

Chevaliers are the second highest level of chiropterans in terms of strength and ability. They are created when a human drinks the blood of a queen. A powerful bond exists between each chevalier and the Queen that sired them, compelling the chevaliers to serve and protect her at all costs. Chevaliers have even greater speed, strength and endurance than regular chiropterans. Though they retain the appearance in body form and age that they had when they were transformed, chevaliers have vast shape-shifting abilities. They can transform into unique forms resembling regular chiropterans, either entirely or limited to specific body parts, and can transform into the humans they have fed upon. They heal instantly from almost any non-lethal wound, though severe wounds will temporarily cause an increase in their need for blood. As with regular chiropterans, chevaliers can be killed with the blood of the opposite queen; however, the crystallization takes longer and it is possible to prevent death by removing the crystallizing body parts. A chevalier can also be killed by beheading or burning their whole body.

Queens, also called the originals, are the first, and highest level, chiropterans. In any given generation, there are always two Queens, who are female twins born from one of the last Queens. Saya and Diva are the current Queens of their species. All chiropterans are born of the blood of Queens, either through the queen's own efforts or human experimentation. Queens appear to retain a human appearance at all times, though they can modify what their human appearance looks like to some degree. Their blood can crystallize and destroy any chiropteran of any level that was created by their sister queen's blood. Queens spend only a few years awake at any given time, between decades of hibernation within a cocoon. Queens have enhanced speed, strength, and endurance that surpasses those of their chevaliers and other chiropterans. They may also have some shape-shifting abilities, though during the series their abilities seem to be limited to modifying to their outward human appearance. The strength of a queen's traits are dependent on their feeding regularly on human blood. As such, Diva, who freely feeds on humans, can also freely use all of her abilities, while Saya, who avoids feeding, is usually only slightly above human level strength. When a Queen becomes pregnant with the next generation of Queens, her blood will lose its dangerous qualities. A queen can only be impregnated by a chevalier created by her sister queen, ensuring the purity of the species.