Never been a Buffy fan, but the only way to not have gotten some familiarity with the show and the accompanying mythos is to have been shut away without a television for the last ten years (or has it been longer). You'd get some just from seeing the commercials for Buffy and Angel.
I'm enjoying this story mainly because it centers around Lois (and I guess you also say Clark), and Shayne is a very talented writer. Even without being fully knowledgeable of the Buffy backstory the 'mystery' and 'problems' that Lois and Clark are confronted with make for interesting reading.
Looking forward to more.
Tank (who thinks it will be interesting to watch Clark's reaction to the more 'bloodthirsty' Lois as her changes take hold)