Hence,P. seroprevalence studies. Keywords:Plasmodium knowlesi, Merozoite surface protein, Recombinant expression, Immunogenicity == Background == Malaria is one of the important infectious diseases that causes high global mortality and morbidity.Plasmodium knowlesihas recently been recognized as the fifthPlasmodiumspecies that can cause malaria in humans [1,2].Plasmodium knowlesireplicates every 24 hours, which is the most rapid replication rate among all humanPlasmodiumspecies. Quoditian fever, hyperparasitaemia, life-threatening complications and death may occur if the patient remains untreated [3]. Proteins expressed on the surface ofPlasmodiummerozoites are promising targets for malaria vaccine development. Merozoite surface protein 1 (MSP-1) is a high molecular mass protein which undergoes two proteolytic steps to produce several fragments. Primary processing occurs during maturation of merozoites, and the secondary processing occurs during the invasion of merozoites into erythrocytes [4-6]. Proteolytic processing of MSP-1 has been intensively studied inPlasmodium falciparum. During the first processing, theP. falciparumMSP-1 precursor polypeptide is cleaved into four major fragments of ~83 kDa (MSP-183), 30 kDa (MSP-130), 38 kDa (MSP-138), and 42 kDa (MSP-142) in size. The secondary processing further cleaves the MSP-142into two fragments, MSP-133and MSP-119. The soluble MSP-133sheds from the merozoite surface [7-9], whereas the membrane-bound MSP-119remains associated with merozoites and is carried into the new erythrocyte during invasion [10,11]. MSP-142is one of Rabbit Polyclonal to Transglutaminase 2 the leading candidates for blood-stage malaria vaccines as it is able to induce protective immune responses [12-14]. Antibodies directed against MSP-142and PF-915275 MSP-119can interrupt merozoite invasionin vitro[15-17]. Children with naturally acquired immune response toPlasmodiumMSP-119are significantly associated PF-915275 with resistance towards malarial infection and clinical manifestations [18], while pregnant women with anti-MSP-119antibodies are protected against placental infection and infection in infants [19]. Immunization studies using MSP-142and MSP-119in animal models such as rodents, mice and primates [20-24] PF-915275 found that protective immune response is elicited during challenge with lifePlasmodiumparasites. MSP-119-mediated protective responses are mainly responsible for humoral immunity. Low prevalence of T cell responses to MSP-119is due to limited T cell epitopes on this fragment.Protective T cell responses, on the other hand, are induced PF-915275 by epitopes on MSP-133[25-27]. MSP-133regulates cell mediated responses inducing effector T cells which help in protective B cells response, cytokines production and antiparasitic activity regulation againstPlasmodiumin an antibody-independent manner [28,29]. It is thus more appropriate to include both MSP-119and MSP-133fragments in the malaria vaccine design in order to elicit both humoral and cell mediated responses. Therefore, MSP-142which has both immunodominant B and T cell epitopes, is considered an important and potential vaccine candidate [30,31]. To date, most of the efforts for development of malaria vaccines and human trials are still focus onP. falciparum. Phase I human vaccine studies by usingP. falciparumMSP-142in USA [32,33], western Kenya [34] and Mali [35] showed high safety, tolerability and immunogenicity, which protective cytokines and antibody responses were detected in the volunteers. However, the raised anti-MSP-142antibodies were insufficient to inhibit parasite growth up to protection level [36,37] and in a Phase II human trial with Kenyan children, the overall vaccine efficacy was considerably low [38]. Nonetheless, the low level protection elicited by this single antigen vaccine could be enhanced and overcome by multi-antigens vaccine development or addition of other immunostimulants. Considerable amount of studies on MSP-142have been carried out on severalPlasmodiumsp. but not much is known aboutP. knowlesiMSP-142, particularly about its immunogenicity. In the present study, a recombinant MSP-142ofP. knowlesi(pkMSP-142) was produced and evaluated using.