ABSTRACT
The vaccine potential of Plasmodium falciparum liver stage antigen-3 (LSA3) was investigated in Aotus monkeys using two long synthetic peptides corresponding respectively to an N-terminal non-repeat peptide (NRP) and repeat 2 (R2) region of the LSA3, adjuvanted by ASO2. Both 100-222 (NRP) and 501-596 repeat peptides induced effector B- and T-cell responses in terms of antigen-driven antibodies and/or specific IFN-gamma secretion. Animals challenged with P. falciparum sporozoites were protected following immunization with either the NRP region alone or the NRP combined with the R2 repeat region, as compared with controls receiving the adjuvant alone. These results indicate that the NRP may be sufficient to induce full, sterile protection and confirm the vaccine potential of LSA3 previously demonstrated in chimpanzees and in Aotus.
Subject(s)
Antibodies, Protozoan/blood , Antigens, Protozoan/immunology , Malaria Vaccines/immunology , Malaria, Falciparum/immunology , Plasmodium falciparum/immunology , Protozoan Proteins/immunology , Animals , Aotidae/immunology , Immunization , Interferon-gamma/biosynthesis , Interferon-gamma/immunology , Malaria, Falciparum/parasitology , Malaria, Falciparum/prevention & control , Peptides/immunologyABSTRACT
Three recombinant proteins spanning the Plasmodium falciparum liver-stage Ag-3 (LSA-3) were used to immunize Aotus monkeys. The proteins were delivered subcutaneously without adjuvant, adsorbed onto polystyrene 0.5 microm particles at a concentration of 2 microg per immunization. Control animals received glutathione-S-transferase formulated similarly. Animals were challenged as late as 5 months after the last immunization, by intravenous inoculation of 100,000 P. falciparum sporozoites of a strain heterologous to the one from which the immunogens were derived. Sterile protection was achieved in three of the five immunized monkeys but in none of four controls. Antibodies were at low titer, but reacted with the native parasite protein and were boosted by parasite challenge. Ag-specific IFN-gamma secretion was detectable in all LSA-3-immunized animals in response to the LSA-3-derived Ag. The protection was apparently associated with high levels of IFN-gamma production in response to in vitro recall Ag. These results lend support to the vaccine potential of LSA-3 indicated by previous results obtained in chimpanzees, as well as the value of yet another Ag-delivery system. They also support the value of the Aotus model for the pre-clinical development of pre-erythrocytic-stage vaccines.