In human sterile immunity against malaria has been obtained only after exposure to irradiated sporozoites inoculated by mosquitoes. The full repertoire of pre-erythrocytic antigens that underlie this sterile protection is not actually known.
The three antigens (CS protein, thrombospondin-related anonymous protein, and Liver stage antigen 3) investigated to-date, as vaccine candidates may not be responsible for induction of optimal protective responses. This would account for the difficulties encountered in reproducing this sterile long-lasting immunity by experimental subunit vaccines based on these antigens. It would clearly be desirable to investigate other pre-erythrocytic antigens. Such efforts to expand targets of pre-erythrocytic stage immunity are justified because the infection is at its most vulnerable during the 5 to 14 days between sporozoite inoculation and the emergence of hepatic merozoites into the blood stream.
During this period two distinct stages (sporozoite and liver stages), whose numbers rarely exceed 100 in the human body; can be efficiently targeted by humoral and cellular immune mechanisms. In the last few years it was discovered that Plasmodium sporozoites express protein members of the EBL and the RH family thought till then to be exclusive to the erythrocytic stages of the parasite. Moreover, sporozoite penetration and/or development can be inhibited by antibodies specific to some of these proteins. This confirms that members of the EBL and RH families may play a functional role during the pre-erythrocytic stages of the malaria infection.
The global objective of this proposal is to establish whether a newly described set of host cell invasion-associated proteins can serve as novel targets of inducible protective immune responses against pre-erythrocytic Plasmodium parasites.
Source: European Commission (Cordis)
