A recombinant baculovirus 42-kilodalton C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 protects Aotus monkeys against malaria

Abstract

The immunogenicity and protective efficacy of a baculovirus recombinant polypeptide based on the Plasmodium falciparum merozoite surface protein 1 (MSP-1) has been evaluated in Aotus lemurinus griseimembra monkeys. The MSP-1-based polypeptide, BVp42, corresponds to the 42-kDa C-terminal processing fragment of the precursor molecule. Immunization of Aotus monkeys with BVp42 in complete Freund's adjuvant resulted in high antibody titers against the immunogen as well as parasite MSP-1. Fine specificity studies indicated that major epitopes recognized by these antibodies localize to conserved determinants of the 19-kDa C-terminal fragment derived from cleavage of the 42-kDa processing fragment. Effective priming of MSP-1-specific T cells was also demonstrated in lymphocyte proliferation assays. All three Aotus monkeys immunized with BVp42 in complete Freund's adjuvant showed evidence of protection against blood-stage challenge with P. falciparum. Two animals were completely protected, with only one parasite being detected in thick blood films on a single day after infection. The third animal had a modified course of infection, controlling its parasite infection to levels below detection by thick blood smears for an extended period in comparison with adjuvant control animals. All vaccinated, protected Aotus monkeys produced antibodies which inhibited in vitro parasite growth, indicating that this assay may be a useful correlate of protective immunity and that immunity induced by BVp42 immunization is mediated, at least in part, by a direct effect of antibodies against the MSP-1 C-terminal region. The high level of protection obtained in these studies supports further development of BVp42 as a candidate malaria vaccine.

Iron oxide nanoparticles as a clinically acceptable delivery platform for a recombinant blood‐stage human malaria vaccine

“…All immunized monkeys produced significant levels of parasite growth inhibitory antibodies, ranging from 55 to 100% inhibition ( Table 2). This level of inhibition is comparable to studies where Aotus monkeys were vaccinated and protected with MSP1-42-CFA (33). Due to the old age of these monkeys, they were not challenged with blood-stage parasites.…”

“…It is possible that rMSP1 delivered via IO nanoparticles induced antibodies that are much more focused toward parasite inhibitory epitopes than antibodies induced by rMSP1-CFA or rMSP1-ISA51, which was reflected in the differences in the degree of in vitro parasite inhibition observed (Table 1). More important, our results showed that in the nonhuman primates, the levels of parasite inhibitory antibodies induced by rMSP1-IO were not only significant (55-100% inhibition) but surpassed or matched those levels previously achieved in MSP1-42-vaccinated and protected monkeys (33).…”

“…Prior studies have demonstrated that the levels of parasite-inhibitory anti-MSP1 antibodies correlate with natural and vaccine induced immunity (32,33,(35)(36)(37)(38)(39). Thus, the presence of anti-MSP1 inhibitory antibodies in the rMSP1-IO vaccinated mice and monkeys were investigated as a measure of in vitro efficacy.…”

“…Immunizations were administered 3 times at 21-d intervals, alternating the right and left thigh. Sera were collected 21 d after the last immunization for ELISAs and parasite growth inhibition assays (33).…”

“…MSP1-42 is found on the surface of the invading merozoites during the erythrocytic stage of the malaria life cycle (28,29) and is one of the most promising and most studied malaria vaccine candidates (30 -34). Protective immunity to malaria infections has been correlated with parasite inhibitory antibodies specific for MSP1-42 (32,33,(35)(36)(37)(38)(39). In this study, outbred mice and Aotus monkeys were immunized with rMSP1 conjugated to IO (rMSP1-IO).…”