What is the best way to seal this old fireplace vent?
Not sure exactly where this vent is, but here in the UK it's pretty much essential to include a vent whenever a fireplace is blocked off.  Otherwise the air inside the chimney goes stale and damp takes effect.  Generally the vent is to the room in which the fire used to be situated.  Just be sure that there is ventilation to the chimney before (more thoroughly) sealing the vent.