The computer being put to sleep is only one of many scenarios in which an application needs to re-acquire an exclusive lock on the Apple IR subsystem. With regards to this, OS X password prompts (or use of secure input fields in applications) as well as screen blankers or display sleep can lead to the same results as if you put your computer to sleep.

The "Universal Mode" in Plex expects to receive button press events through the Apple IR subsystem, which is what the Virtual Remote will forward button presses to when you use the Virtual Remote actions. If you want to use that Plex mode with a Harmony remote that uses the Plex profile supplied by Plex Inc, then that's what you should use, yes.

However, all the Virtual Remote does (and technically can do) is forward button presses to the Apple IR subsystem. What happens with it there is outside of Remote Buddy's sphere of control. Instead, whoever currently has gained exclusive control from OS X will get ALL button press events. Those who couldn't get exclusive access, however, will get no events at all.

I see that you use another tool (Prismatik) that wants access to the Apple IR subsystem and - at least at the time you took the screenshot - also has gained access to the Apple IR subsystem while the "Plex Helper" (that Plex uses to receive Apple IR events) either didn't run or didn't get access to the Apple IR subsystem, as it is not part of the list displayed by Remote Control Diagnostics.

Since you can always access Remote Buddy's menu and the Virtual Remote will thus also be able to reliably forward Apple Remote button press events to the Apple IR subsystem, the problem on your Mac appears not to be with Remote Buddy, but with the communication/connection between Apple's IR subsystem and the Plex Helper that connects to that subsystem.

Possible solutions (each on its own or a combination): 
1) Quit Prismatik (or disable its Apple Remote functionality, if that's possible) 
2) Make sure the Apple Remote support in Plex is "always enabled" (I usually wouldn't recommend this option, as other apps will not be able to use the Apple IR subsystem even when Plex isn't running, but in your case Plex seems to be your primary use case)

At any time, you can use Remote Control Diagnostics to determine the current status of your system and peek under the hood of the Apple IR subsystem and see which app currently has access to it - and which don't (by being absent).

Best regards, 
Felix Schwarz