Abstract. Leishmania Viannia strains from 1,092 patients who acquired dermal leishmaniasis in endemic regions of Colombia were analyzed for expression of species and subgenus specific epitopes. Eight monoclonal antibodies prepared against membranes of the major species of the Viannia subgenus and previously shown to distinguish these species, recognized low molecular mass (< 45kD) membrane components. Thirteen widely but non-uniformly distributed serodemes were identified: one unique to L. panamensis, four unique to L. braziliensis and eight that were common to L. braziliensis and L. guyanensis. Thirty-seven percent of Colombian L. braziliensis strains concomitantly typed by isoenzymes were null, i.e., not recognized by the corresponding species-specific B-16 or B-18 antibodies. No Colombian L. guyanensis strains were recognized by the antibody specific for this species (B-19). In contrast, L. panamensis-specific B-4 and B11 antibodies recognized > 98% of the L. panamensis strains. Null strains of L. braziliensis and L. panamensis were more frequently isolated from mucosal leishmaniasis than strains that expressed species specific epitopes, suggesting that these strains may be more pathogenic.

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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 ? m particles at a concentration of 2 ? g 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-+ 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-+ 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 preerythrocytic-stage vaccines.

Using newer vaccine platforms which have been effective against malaria in rodent models, we tested five immunization regimens against Plasmodium knowlesi in rhesus monkeys. All vaccines included the same four P. knowlesi antigens: the pre-erythrocytic antigens CSP, SSP2, and erythrocytic antigens AMA1, MSP1. We used four vaccine platforms for prime or boost vaccinations: plasmids (DNA), alphavirus replicons (VRP), attenuated adenovirus serotype 5 (Ad), or attenuated poxvirus (Pox). These four platforms combined to produce five different prime/boost vaccine regimens: Pox alone, VRP/Pox, VRP/Ad, Ad/Pox, and DNA/Pox. Five rhesus monkeys were immunized with each regimen, and five Control monkeys received a mock vaccination. The time to complete vaccinations was 420 days. All monkeys were challenged twice with 100 P. knowlesi sporozoites given IV. The first challenge was given 12 days after the last vaccination, and the monkeys receiving the DNA/Pox vaccine were the best protected, with 3/5 monkeys sterilely protected and 1/5 monkeys that self-cured its parasitemia. There was no protection in monkeys that received Pox malaria vaccine alone without previous priming. The second sporozoite challenge was given 4 months after the first. All 4 monkeys that were protected in the first challenge developed malaria in the second challenge. DNA, VRP and Ad5 vaccines all primed monkeys for strong immune responses after the Pox boost. We discuss the high level but short duration of protection in this experiment and the possible benefits of the long interval between prime and boost.