Hi Swen,
One way is to trigger based off a change in Lead Status. I'm not sure how your company uses that field, but if their status is switched to "Engaged," or something equivalent, you can base it off of that.
Added to Opportunity would work, but is everyone who responds added to an Opportunity? You can do based on activity logged, but you would need to make sure there is a consistent naming convention on the activity so that the trigger can pick it up.
Can you describe the process for the rep if a prospect responds?