Every Class B camper I looked at when designing mine, was hard mounted to the cab. I'm not sure how much the frames flex, but when you compare a E350 frame to a MDT or HDT I would guess the frame flexes less then the E350.
There are many many 25-30 year old Mini homes (class B's) sitting on used dealer lots they all seem to have age issues, but cab to box seals are not one of them.
Thats when I decided to hard mount mine. I securely bolted my cab to the frame, to eliminate the rubber mount flex, then we welded the side panels directly to the cab. There may be an easier way, but I couldn't come up with one.