In Blade II, Blade is recruited by the Vampire Nation to help stop the Reaper threat. The Reapers are a new breed of vampire, infected with a virus that transforms them into unstoppable killing machines with a thirst for both human and vampire blood. The Vampire Nation fears that if the Reapers are not stopped soon, they will spread to all of the vampire clans and cause a global epidemic that could wipe out all life on Earth.
To fight the Reapers, Blade teams up with a group of vampire warriors called the Bloodpack. Led by the ruthless Reinhardt and containing such lethal members as Nyssa, Snowman, and Chupa, the Bloodpack is initially hostile to Blade and his human ally Whistler. However, with the help of Nyssa - daughter of the Vampire Nation's leader - Blade convinces the Bloodpack that the Reaper threat is too great to ignore.
Together, Blade and the Bloodpack infiltrate the vampire stronghold known as the House of Pain, where the Reapers are believed to be hiding. After a brutal battle, Blade and the Bloodpack capture a live Reaper and come up with a plan to extract the virus from its blood so they can create a vaccine and stop the plague.
However, the plan goes awry when it turns out that the Reaper they captured is actually a genetically-engineered "Uber-Reaper" designed to be even more powerful than the others. To defeat it, Blade must use all of his skills and team up with even more unlikely allies - including a rogue vampire named Scud and a terminally-ill scientist named Karen - to conquer the unstoppable beast and save humanity from extinction.