Experimental infection and protection against ... - TI Pharma

Introduction 17
Figure 4. Population indices of immunity to malaria in Kilifi, Kenya. [53]
expressed on the surface of infected erythrocytes and are essential for
adherence of the parasite to vascular endothelium to avoid destruction in the
spleen [11, 44]. As one parasite clone expressing one PfEMP1 is detected by the
immune system, another parasite clone expressing another PfEMP1 takes over.
Despite its diversity, efforts are undertaken to identify conserved domains or
induce antibodies against PfEMP1s, since these antigens are responsible for
specific disease manifestations such as placental or cerebral malaria [45, 46].
Placental malaria is mediated by parasites expressing a specific variant surface
antigen, var2CSA [47]. Acquired immunity to placental malaria in multigravid
women corresponds with acquisition of var2CSA-specific antibodies [48].
Transmission blocking vaccine candidates
Transmission Blocking Vaccines consist of molecules eliciting the production of
antibodies that will interfere with the parasite development in the mosquito.
Four Pf antigens have attracted most attention as potential components of
mosquito stage vaccines: gametocyte/gamete antigens Pfs230 and Pfs48/45 and
zygote/ookinete antigens Pfs25 and Pfs28. Naturally occurring antibodies
directed against these proteins can be found in people living in endemic areas
[49, 50]. Nonetheless, these antigen targets show very limited sequence
diversity compared to blood stage antigens. A major practical difficulty has
been in expressing the proteins in the correct conformation to achieve
immunogenicity [51]. A phase I trial of Pfs25 in healthy human volunteers was
halted prematurely because of systemic reactogenicity [52].