do you mean 4.5 agents of a separate ePo 4.5 system (other than ePo 4.0 that you refer to here)?
Otherwise ePo 4.0 can handle MA 4.5 clients and updating should be just fine...
the 4.5 agents are in a different managed system, but they will update from a 4.0 repository. does that make sense??
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I guess some items in the ePo 4.0 repository might not be wanted to be seen and aqcuired by the 4.5 agents, such as the McAfee Agent installer (I never tried it with different major version levels, but I feel a slight chance here that 4.5 clients might be reconfigured to use ePO 4.0 management if they run a deployment task for McAfee Agent) and if the two system must have different patch levels for VSE then you need to check if ePO 4 repository does not contain higher VSe patch than the other, etc.
We have a similar scenario here at our organization, but with ePO 4.0 agents updating from a ePO 4.5 repository (selective and local repository).