The immunogenicity and efficacy of a hybrid
recombinant protein derived from the N-terminal end of the
glutamate-rich
protein (GLURP) and the C-terminal portion of the merozoite
surface protein 3 (MSP3) of Plasmodium falciparum was evaluated in Saimiri sciureus monkeys. The GLURP/MSP3 hybrid
protein, expressed in Lactococcus lactis, was administered in association with
alum,
Montanide ISA720, or complete or incomplete
Freund adjuvant (CFA/IFA) in groups of five animals each. The three formulations were shown to be immunogenic, but the one with
alum was shown to be weak compared to the other two, particularly CFA/IFA, which provided very high antibody titers (
enzyme-linked
immunosorbent assay titers of >3,000,000 and immunofluorescence antibody test titers of 6,400). After a challenge
infection with P. falciparum FUP strain, all five monkeys from the GLURP/MSP3-
alum group showed a rapid increase in
parasitemia, reaching 10% and were treated early. The two monkeys with the highest antibody titers in group GLURP/MSP3-
Montanide ISA720 had a delay in the course of
parasitemia and were treated late due to a low hematocrit. In the GLURP/MSP3-CFA/IFA group,
parasitemia remained below this threshold in four of the five animals and, after it reached a peak,
parasitemia started to decrease and monkeys were treated late. When all animals were grouped according to the outcome, a statistically significant association between high antibody titers and partial protection was observed. The challenge
infection boosted the antibody titers, and the importance of this event for
vaccine efficacy in areas where this parasite is endemic is discussed. In conclusion, these data suggest that GLURP and MSP3 can induce protection against
malaria infection if
antibodies are induced at properly high titers.