Is this machine behind any barriers such as a company or university firewall or proxy server?
Also, do you have any other protection software active?
How do you connect to the internet?
Make sure that you haven't accidentally disabled updating.
Double-click the taskbar icon to open Security Center
Click Advanced Menu (bottom left)
Click Configure (left)
With Security Center highlighted at top left, click Advanced over at the right.
Make sure anything but the last option in the attached thumbnail #1 are checked - choose the best for you.
(Click thumbnail to enlarge).
Even if you don't use Internet Explorer.......
Get rid of IE8 beta, if you have it. In IE7 go to Tools/Internet Options/Advanced and click the "Reset" button.
Close and re-open IE7 and re-enable the add-ons under Tools/Manage Add-Ons.
Go to Start/Run and enter services.msc and click Enter. OK UAC if it prompts.
Make sure the McAfee services are all started and automatic except possibly Scanner as shown in thumbnail #3.
(Note: the number of services will vary depending on your installed products).
There is something else you could try which involves deleting some files and replacing them.
First, in Windows Explorer (any internal page such as Documents) go to Tools/Folder Options/View and make sure that "Show Hidden Files & Folders" is enabled as in thumbnail #2. Click Apply and OK.
Go to your drive\Program Files\McAfee\VirusScan\DAT and delete the contents of that folder. Take care to delete only the contents and not the folder itself.
Your Security Center should now be throwing up errors. Right-click the taskbar icon and select Updates.
Lastly make sure that Windows is totally up to date with all critical and non-critical updates using the Microsoft Updates option in Vista.