Most likely either an NTFS or an IIS-permisions issue.
Check your IIS log for errors (4xx usually is permissions problems).
Alternatively, running FILEMON or PROCMON (though this is more spammy), you can find what files are throwing the deny, and work off of that.
It'll be a big help if you have a healthy (often a test system) Core available to cross-check what the NTFS / IIS-permissions need to be.
- Paul Hoffmann
LANDesk EMEA Technical Lead