It is worth noting however, that this is not unprecedented as several studies reported that some domains of PfEMP1-Var2CSA failed to induce surface reactive antibodies. Several lines of evidence indicate that iRBC-displayed surface Sumanirole Maleate epitopes are disulfide bond dependent, conformational epitopes. VarO-iRBC surface reactivity was correlated with reactivity on immunoblot of non-reduced parasite extracts and some surface-reacting polyclonalser a failed to react on immunoblots of reduced parasite antigens. In contrast, the anti-eDBL0 antisera failed to react on immunoblots of unreduced parasite antigens and failed to react with the VarO-iRBC surface. This indicates that the urea-denatured protein, which moreover lacks the functionally essential NTS domain does not present surface-displayed epitopes. Likewise, antisera raised to the reduced-alky lated eDBL1RA or eDBL2RA failed to react with the iRBC surface and failed to react on immunoblot of unreduced parasite extracts. This is in line with results showing that antisera against denatured iodoacetamide treated-Var2CSA DBL5 failed to react with the surface of Var2CSA expressing parasites, while antisera to the native domain did so. The crystal structure of VarO-DBL1 and VarO-Head shows numerous disulfide bonds that shape protein surface areas with nonlinear sequence fragments. It is thus no surprise that surface epitopes depend on the proper formation of disulfide bonds. It is unlikely that such epitopes will be mimicked by synthetic peptides, although some success has been reported in rats immunised with a specific peptide sequence of subdomain2 of PfEMP1-DBL1��. Efficient cytoadherence inhibition/disruption was observed only with antibodies toDBL1 and to the Head domain, and inhibition/disruption by anti-CIDR andanti-DBL2antibodies antibodies was modest. Thus, the capacity to elicit antibodies interfering with rosetting seems restricted to few PfEMP1-VarO domains and is a property of the RBC (-)-Huperzine A adhesion domain.This differs from the situation reported for the rosette-forming variant IT4-R19 in which antibodies to NTS-DBL1 as well as antibodies to DBL2C2 potently reversed rosette formation and more over antibodies to five individual domains inhibited rosette formation.