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Good question stsobiec. I'm interested in this also.
What version of McAfee AntiSpyware are you pushing out?
I'm using the same version.
Ok - I'll start with what i know.....
Here are the base settings to at least scan for spyware and prevent(hopefully) it.
1. Enable the unwanted programs policy
2. Enable the on-access scanner for unwanted programs
3. Enable detection of unwanted programs during scanning
And lastly, and here is where most of my concerns are, define AntiSpyware Access Protection, Common Standard and Common Maximum Protection rules. Within my organization(higher ed), we cannot completely lock down a machine as it would hinder people's ability to teach/work/learn. Ultimately, we want to provide as much protection without hindering the installation of legitimate software such as activeX controls.
Recommendation: Make sure you DON'T set the "Alert when a cookie detection occurs" under On-Access Scan Settings > Messages
This can generate a lot of alerts and cause your ePO server to fall over because the Event Parser won't be able to cope.