Can't protect Item Frame contents by any means that I know of any longer.

LWCEntityLocking allows locking of item frames.  – The frame is "locked" and will alert you that it is "locked by a magical spell" if you try to break the frame... but the item inside is fair game, anyone can take it, regardless of permission level.

WorldGuard regions – will prevent build and any modification to an item frame... normally.  But as of more recent build... while still giving the message "You can't change this here!" the item will still pop out of the frame as if this protection was not in place.

GriefPrevention – applies similar protection to placed blocks within any defined "claim" as WorldGuard does.  Again... the item frame itself cannot be broken... but the item inside... welp, anyone can just walk by and punch it to remove it.

All three of these protections worked prior to the build I assembled yesterday... changes which involved nothing in regards to item frames that I could tell from their descriptions so... what did you do?