I have started to see sporadic problems whit the Adobe reader plug-in in Internet Explorer 11.
The problem is that the plug-in will at some point in time be added to a registry key blocking the plug-in:
Deleting the key or if the user disables and then enables the plugin (which will also delete the key in question), then the plugin will work again.
I have only seen this problem on Windows 7 x64 with Internet Explorer 11 and System Center Endpoint Protection active, so it seems to be related to Endpoint Protection. But there could be other combinations with the same problem.
This could very well be related to Extension validating in Internet Explorer 11 https://msdn.microsoft.com/en-us/library/dn301826.aspx but only guessing.
Right now the quickest way to stop the frustration for users is to use Group Policy Preferences, Desired Configuration or script to get rid of the key on a regular basis.
It also seems to work to stop Internet Explorer from using the Extension Validation but this might lead other problems.
Let hope it will be fixed by Microsoft or Adobe or that we find a better solution to deal with the problem.