immunity to PAM. However, the findings reported here and elsewhere also suggest that var2csa diversity (Duffy et al., 2006a; Trimnell et al., 2006) is driven by protective immunity to PAM, a situation that may complicate development of VAR2CSAbased vaccines against PAM (Beeson et al., 2006) . IE adhesion to CSA, which is thought to be a critical element in the pathogenesis of PAM (Fried and Duffy, 1996) , is mediated by VAR2CSA as documented by recent knockout studies (Viebig et al., 2005; Duffy et al., 2006b) , and several CSA-adhesive domains have been identified in the antigen (Gamain et al., 2005) . Recent studies in mice suggest that vaccination can elicit broadly reactive antibodies that can block VAR2CSAdependent IE adhesion to CSA (Gamain et al., 2004; Bir et al., 2006) , but whether such antibodies are ever produced in humans in response to PAM, how clinically relevant they are, and whether they can be induced by vaccination in humans remain unanswered questions.