This might be a stupid question but are you purging all the air out of your vacumn hose and making sure it is filled with water before you connect it to the skimmer?
Your pump is losing prime. When you open the main drain it fills with water and regains prime. I am not clear from your post if the loss of prime also occurs if you just shut the drain and have only the skimmer active or if it happend when you hook up the hose and try to vacumn. If it only occurs when you have the vacumn connected I would suspect that you have not purged the vacumn hose of air. If it occurs when you shut the main drain and only have the skimmer going BEFORE you connect the vacumn hose then I would suspect a suction side leak somewhere in your skimmer line.