While the logical meaning is the same with or without the comma, without it, the reader may feel like he doesn't know one thing:
[ 異変とその影に潜む陰謀 ] を、彼はまだ知らない。
With the comma, it is much clearer that 彼 doesn't know two things:
[ 異変 ] と、 [ その影に潜む陰謀 ] を、彼はまだ知らない。
It just emphasizes the 異変 more, and I think the pause matches the way a tasteful narrator would read the sentence out loud. I'd say the difference is similar to these two sentences:
- He has yet to discover the anomaly, and the conspiracy behind it.
- He has yet to discover the anomaly and the conspiracy behind it.