Hundreds of years after Armageddon, the tension between Methuselahs (vampire-like creatures) and Terrans (humans) continues. Terrans are led and protected by the Holy Roman Empire, of which the capital is Vatican, while the Methuselah are backed by Byzantine. A third major player, Albion, is known for its manufacture of war technology. It is a predominantly human colony but independent of Vatican's control.
At the start of the anime adaptation, the Terrans and Methuselahs are in a standstill. Viewers are introduced to Abel Nightroad, a member of the AX Agency, Caterina Sforza's special operations group. At the outset she is shown at odds with Francesco di Medici, a cardinal in the Vatican, who wants to start a war and is trying to intimidate young Pope Alessandro XVIII to do so.
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Caterina's goal to have diplomatic relations with the Byzantine Empire is carried out secretly with the help of the AX agents. It seems that a more grievous threat is about to reveal itself and they suspect that a fourth party, the Rosenkreuz Order is orchestrating a war.