i haven't read the books or manga myself but from my understanding, Vampires/Methuselah were human colonists sent to Mars where the contracted the "Bacillus Virus" which is a Martian Virus, if there was life on Mars before humans arrived it could have been the cause of Martian Extinction though i'm not sure if it's a natural virus, engineered virus or a virus born from dead Martian's who evolved to be vampires but there doesn't seem to be any indication that the Bacillus Virus was alien in nature to Mars (ie. having came from somewhere else in the universe).
Crusniks Nanomachines were also found on Mars and if the Bacillus Virus is connected to Martian Vampires, then the Crusniks Nanomachines may have been made as a weapon to use against them as we know Crusniks feed on Vampires and are by far more powerful.
As for the concept of space/aliens that's what the Methuselah are to the Terrans in the very beginning as they where Humans who were changed on Mars and came back to wage war so in a sense they are aliens, the Ships we see at the beginning of the anime series is more than likely space ships from Mars at the beginning of the war.
Also in the anime the scenes we see Able, Cain, Seth anbd Lilith on a spaceship looking over Earth and at the end we see it. this ship is called Ark and i think in the novels it's covered again, see bellow (major spoiler)
The Vatican destroy's the Empire's second largest City with a nuclear attack, Seth goes to reactive the Ark hoping to use it's Satellite Cannon to destroy the Vatican's nuclear launch facility
Cain and Dietrich appear and take control of the Ark and it's revealed Cain plans to crash it into the earth and Able gets involved with the fight between Cain and Seth
Seth is able to stop Cain's plan but is weakened where Cain then severs her head, killing her. the Order of Rosenkreuz twists the information framing Able for Seth's Murder and since Seth was the Empress Augusta Vradica, seen as the "Mother" of the Methuselah, and Able is allied with the Vatican the Empire starts and all out war with the Terrans
though i'm not sure if the above takes place in Rages Against the Moons or Reborn on the Mars