After a few more tests, reading, and banging my head against the wall until I saw "the light", I was able to make it work using -not instead of prune. Then was I was able to get rid of the -o print at the end (if someone can still explain what that is, it's always good to learn something new.
find "$KMVAR_Local__mainDir" -type f -mmin -15 -not -path "/Users/dannywyatt/My Files/Tests/Keyboard Maestro Tests/_Template with multiple files and folder/skip/*"
It seems that the small, but important issue, was that I wasn't adding /* at the end. Once I did, it started working.
I don't know why it doesn't work the same way using prune though.