Efficacy of vaccines containing rhoptry-associated proteins RAP1 and RAP2 of Plasmodium falciparum in Saimiri boliviensis monkeys.

Abstract

Abstract. A vaccine trial was conducted with rhoptry-associated proteins 1 and 2 (RAP1 and RAP2) of Plasmodium falciparum in Saimiri boliviensis monkeys to compare the ability of parasite-derived (PfRAP1 and 2) and recombinant proteins (rRAP1 and 2) to induce protective immune responses and to find adjuvants suitable for use in humans. Eight groups of 6 monkeys each were immunized with parasite-derived or recombinant RAP1 and 2 with Freund's complete adjuvant (FCA) followed by Freund's incomplete adjuvant (FIA), Montanide ISA720 adjuvant, or CRL1005 adjuvant. Recombinant RAP1 and RAP2 were also administered separately, with Montanide ISA720. After 3 immunizations, monkeys were challenged by iv inoculation of 50,000 parasites of the Uganda Palo Alto strain of P. falciparum. Of the animals vaccinated using FCA/FIA, 1 of 6 control monkeys, 3 of 6 immunized with PfRAP1 and 2, and 2 of 6 with rRAP1 and 2 did not require drug treatment. Of the monkeys vaccinated with Montanide ISA720 adjuvant, 0 of the 6 control monkeys, 2 of 6 immunized with RAP1 and 2, 1 of 6 immunized with rRAP1, and 4 of 6 immunized with RAP2 did not require drug treatment. Two of 6 monkeys immunized with PfRAP1 and 2 with CRL1005 did not require treatment. All groups receiving RAP1, RAP2, or both had a significant decrease in initial parasite multiplication rates and there was a significant negative correlation between anti-RAP2 antibody and multiplication rates. Animals were rechallenged with the homologous parasite 126 days after the first challenge. Of the monkeys that did not require drug treatment after the first challenge, none developed detectable parasitemia following rechallenge.

A Modified Hepatitis B Virus Core Particle Containing Multiple Epitopes of thePlasmodium falciparumCircumsporozoite Protein Provides a Highly Immunogenic Malaria Vaccine in Preclinical Analyses in Rodent and Primate Hosts

“…Malaria CS synthetic peptide vaccines or recombinant blood stage vaccines adjuvanted with Montanide ISA 720 have shown promising results in nonhuman primates and phase I clinical studies (1,7,14,20,40). Immunization protocols in which primary doses with vaccine formulated in Montanide ISA 720 are followed with a booster inoculation containing the same antigen in a different adjuvant have reduced reactogenicity noted with some antigenMontanide ISA 720 formulations (39,49).…”

Interaction of HLA and Age on Levels of Antibody toPlasmodium falciparumRhoptry-Associated Proteins 1 and 2

“…In addition, protein preparations containing both RAP1 and RAP2 have been used to immunize Saimiri monkeys. In these studies, the immunized monkeys developed a lower peak parasitemia than nonimmunized controls and were protected from subsequent lethal blood-stage challenge with P. falciparum (9,30,32,34) in a way similar to the protection acquired by immunization with whole merozoite (27,39,46). Two rhoptry-associated proteins, RAP1 and RAP2, have been sequenced (20,36).…”

“…The rhoptry-associated proteins 1 and 2 (RAP1 and RAP2) form a low-molecular-mass complex located in the rhoptries of Plasmodium falciparum (5,9). The rhoptries are a pair of organelles at the apical end of the parasite that are involved in the invasion of erythrocytes; thus, molecules in the rhoptries were among the first components identified as potential candidates for a subunit vaccine.…”

“…Unlike many other P. falciparum antigens, RAP1 and RAP2 exhibit a high degree of sequence similarity among P. falciparum isolates. Isolates from Honduras, Sierra Leone, Tanzania, India, Thailand, The Netherlands, Uganda, and Vietnam have been sequenced for RAP1, and isolates from Honduras, Papua New Guinea, The Netherlands, Uganda, and Vietnam have been sequenced for RAP2 (9,20,21,33,36). Thus, it is thought likely that RAP1 and RAP2 proteins may provide a relatively isolate-independent protective immunity in humans compared to other P. falciparum antigens.…”

Members of the Low‐Molecular‐Mass Rhoptry Protein Complex ofPlasmodium falciparumBind to the Surface of Normal Erythrocytes

“…Some MAbs developed against RSP-2/RAP-2 and RAP-1 have been shown in vitro to inhibit parasite invasion [4,14]. Vaccine trials with RAP-1 and RAP-2 were conducted in different Saimiri monkey models [15]. They showed promising results, with lower peaks of parasitemia in immunized monkeys than in control monkeys and protection from subsequent challenge.…”