I'm using Sibelius 5.2, VDL 2.5, on a Mac.  When using my keyboard for input (M-Audio|Key Studio), it inputs either a step above or a third above the key I press, depending on the octave.  (i.e. if I hit the F key, it inputs on the G-line or A-space, depending on the octave)

My first guess would be that your M-Audio keyboard may need to be reset. I think it's possible that sometimes the octave + or - buttons can affect transpositions in half steps depending on what buttons have been pressed before they're initiated. Check the documentation for your M-Audio keyboard about doing a full reset of the device, and see if that helps.

It could also be a transposing instrument in the score. 

I'm gonna think Jim's guess is right. I've had the same problem a few times with my Axiom 49 and doing a restart of Sibelius and unplugging the keyboard seemed to fix the problem. Could be that a button got bumped or something of that nature.

Let us know how you get on.