I tried to use & in the signature for a method in defprotocol. Apparently (see below), this is compiled so that & becomes a simple parameter name, and there is no special handling for variable number of parameters. I think the use of & in a protocol signature ought to be detected and immediately cause an exception (I also think this restriction on the signatures ought to be documented; I couldn't find it specified in the current documentation, though of course it is implied (as I later realized) by the fact that defprotocol creates a Java interface).
user=> (defprotocol Applier (app [this f & args]))
user=> (deftype A  Applier (app [_ f & args] (prn f & args) (apply f args)))
user=> (app (A.) + 1 2)
#<core$PLUS clojure.core$PLUS@5d9d0d20> 1 2
IllegalArgumentException Don't know how to create ISeq from: java.lang.Long