Publications by authors named "Robert W Moon"

Article Synopsis
  • * These parasites depend on specialized cytoskeletal structures for their shape, replication, and movement across tissues, with recent research using advanced technologies providing new insights.
  • * The review highlights recent findings in cytoskeletal biology of these parasites compared to typical model organisms and points out ongoing research questions, particularly involving key species that affect human health.
View Article and Find Full Text PDF

Recent data indicate increasing disease burden and importance of Plasmodium vivax (Pv) malaria. A robust assay will be essential for blood-stage Pv vaccine development. Results of the in vitro growth inhibition assay (GIA) with transgenic P.

View Article and Find Full Text PDF
Article Synopsis
  • The study focuses on two closely related malaria parasites that infect humans, investigating the role of a specific protein, MTRAP, essential for their invasion of human red blood cells.
  • Through a series of experiments, researchers expressed MTRAP proteins, analyzed immune responses, and found that antibodies against these proteins can inhibit parasite invasion.
  • The findings suggest that MTRAP could be a valuable target for creating vaccines and treatments for both vivax and knowlesi malaria.
View Article and Find Full Text PDF

The zoonotic malaria parasite is an important public health concern in Southeast Asia. Invasion of host erythrocytes is essential for parasite growth, and thus, understanding the repertoire of parasite proteins that enable this process is vital for identifying vaccine candidates and how some species are able to cause zoonotic infection. Merozoite surface protein 1 (MSP1) is found in all malaria parasite species and is perhaps the most well-studied as a potential vaccine candidate.

View Article and Find Full Text PDF

Background: Plasmodium vivax has been more resistant to various control measures than Plasmodium falciparum malaria because of its greater transmissibility and ability to produce latent parasite forms. Therefore, developing P. vivax vaccines and therapeutic monoclonal antibodies (humAbs) remains a high priority.

View Article and Find Full Text PDF

Invasion of red blood cells (RBCs) by Plasmodium merozoites is critical to their continued survival within the host. Two major protein families, the Duffy binding-like proteins (DBPs/EBAs) and the reticulocyte binding like proteins (RBLs/RHs) have been studied extensively in P. falciparum and are hypothesized to have overlapping, but critical roles just prior to host cell entry.

View Article and Find Full Text PDF

There are no licensed vaccines against . We conducted two phase 1/2a clinical trials to assess two vaccines targeting Duffy-binding protein region II (PvDBPII). Recombinant viral vaccines using chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) vectors as well as a protein and adjuvant formulation (PvDBPII/Matrix-M) were tested in both a standard and a delayed dosing regimen.

View Article and Find Full Text PDF

The symptoms of malaria occur during the blood stage of infection, when the parasite replicates within human red blood cells. The human malaria parasite, Plasmodium vivax, selectively invades reticulocytes in a process which requires an interaction between the ectodomain of the human DARC receptor and the Plasmodium vivax Duffy-binding protein, PvDBP. Previous studies have revealed that a small helical peptide from DARC binds to region II of PvDBP (PvDBP-RII).

View Article and Find Full Text PDF

The Duffy antigen receptor for chemokines (DARC) expressed on erythrocytes is central to (Pv) invasion of reticulocytes. Pv expresses a Duffy binding protein (PvDBP) on merozoites, a DARC ligand, and their protein-protein interaction is central to vivax blood stage malaria. Here we compared the functional activity of humAbs derived from naturally exposed and vaccinated individuals for the first time using easily cultured (Pk) that had been genetically modified to replace its endogenous PkDBP orthologue with PvDBP to create a transgenic parasite, PkPvDBPOR.

View Article and Find Full Text PDF

The zoonotic Plasmodium knowlesi parasite is a growing public health concern in Southeast Asia, especially in Malaysia, where elimination of P. falciparum and P. vivax malaria has been the focus of control efforts.

View Article and Find Full Text PDF

The lack of a long-term in vitro culture method has severely restricted the study of Plasmodium vivax, in part because it limits genetic manipulation and reverse genetics. We used the recently optimized Plasmodium cynomolgi Berok in vitro culture model to investigate the putative P. vivax drug resistance marker MDR1 Y976F.

View Article and Find Full Text PDF

Several unrelated classes of antimalarial compounds developed against Plasmodium falciparum target a parasite-specific P-type ATP-dependent Na pump, PfATP4. We have previously shown that other malaria parasite species infecting humans are less susceptible to these compounds. Here, we generated a series of transgenic Plasmodium knowlesi orthologue replacement (OR) lines in which the endogenous locus was replaced by a recodonized atp4 () coding region or the orthologous coding region from P.

View Article and Find Full Text PDF

Synchronisation of Plasmodium cultures is essential to investigate the complexities of time-dependent events associated with the asexual blood stage of the malaria parasite life cycle. Here we describe a procedure using ML10, a highly specific inhibitor of the parasite cyclic GMP-dependent protein kinase (PKG), to attain high synchronicity of Plasmodium falciparum and P. knowlesi asexual blood-stage cultures and to obtain high levels of arrested mature schizonts as well as viable released merozoites.

View Article and Find Full Text PDF

, a malaria parasite of Old World macaque monkeys, is used extensively to model biology. Recently, was found in the human population of Southeast Asia, particularly Malaysia. causes uncomplicated to severe and fatal malaria in the human host with features in common with the more prevalent and virulent malaria caused by .

View Article and Find Full Text PDF

Background: There are no licensed vaccines against , the most common cause of malaria outside of Africa.

Methods: We conducted two Phase I/IIa clinical trials to assess the safety, immunogenicity and efficacy of two vaccines targeting region II of Duffy-binding protein (PvDBPII). Recombinant viral vaccines (using ChAd63 and MVA vectors) were administered at 0, 2 months or in a delayed dosing regimen (0, 17, 19 months), whilst a protein/adjuvant formulation (PvDBPII/Matrix-M™) was administered monthly (0, 1, 2 months) or in a delayed dosing regimen (0, 1, 14 months).

View Article and Find Full Text PDF

malaria parasites are obligate intracellular protozoans that use a unique form of locomotion, termed gliding motility, to move through host tissues and invade cells. The process is substrate dependent and powered by an actomyosin motor that drives the posterior translocation of extracellular adhesins which, in turn, propel the parasite forward. Gliding motility is essential for tissue translocation in the sporozoite and ookinete stages; however, the short-lived erythrocyte-invading merozoite stage has never been observed to undergo gliding movement.

View Article and Find Full Text PDF

Plasmodium lactate dehydrogenase (pLDH) is a common target in malaria rapid diagnostic tests (RDTs). These commercial antibody capture assays target either Plasmodium falciparum-specific pLDH (PfLDH), P. vivax-specific pLDH (PvLDH), or a conserved epitope in all human malaria pLDH (PanLDH).

View Article and Find Full Text PDF

Several promising antimalarial drugs are currently being tested in human trials, such as artefenomel, cipargamin, ferroquine and ganaplacide. Many of these compounds were identified using high throughput screens against a single species of human malaria, Plasmodium falciparum, under the assumption that effectiveness against all malaria species will be similar, as has been observed for other antimalarial drugs. However, using our in vitro adapted line, we demonstrated recently that P.

View Article and Find Full Text PDF

Malaria remains a major cause of morbidity and mortality globally. Clinical symptoms of the disease arise from the growth and multiplication of parasites within the blood of the host. Thus assays to determine how drug, antibody and genetic perturbations affect the growth rate of parasites are essential for the development of new therapeutics and improving our understanding of parasite biology.

View Article and Find Full Text PDF

is a zoonotic malaria parasite in Southeast Asia that can cause severe and fatal malaria in humans. The main hosts are Macaques, but modern diagnostic tools reveal increasing numbers of human infections. After is the only other malaria parasite capable of being maintained in long term culture with human red blood cells (RBCs).

View Article and Find Full Text PDF

During the course of the asexual erythrocytic stage of development, Plasmodium spp. parasites undergo a series of morphological changes and induce alterations in the host cell. At the end of this stage, the parasites egress from the infected cell, after which the progeny invade a new host cell.

View Article and Find Full Text PDF

Malaria is caused by multiple different species of protozoan parasites, and interventions in the pre-elimination phase can lead to drastic changes in the proportion of each species causing malaria. In endemic areas, cross-reactivity may play an important role in the protection and blocking transmission. Thus, successful control of one species could lead to an increase in other parasite species.

View Article and Find Full Text PDF

The efficacy of current antimalarial drugs is threatened by reduced susceptibility of to artemisinin, associated with mutations in Another gene with variants known to modulate the response to artemisinin encodes the μ subunit of the AP-2 adaptin trafficking complex. To elucidate the cellular role of AP-2μ in , we performed a conditional gene knockout, which severely disrupted schizont organization and maturation, leading to mislocalization of key merozoite proteins. AP-2μ is thus essential for blood-stage replication.

View Article and Find Full Text PDF

Quinolones, such as the antimalarial atovaquone, are inhibitors of the malarial mitochondrial cytochrome complex, a target critical to the survival of both liver- and blood-stage parasites, making these drugs useful as both prophylaxis and treatment. Recently, several derivatives of endochin have been optimized to produce novel quinolones that are active and in animal models. While these quinolones exhibit potent activity against and , their activity against the zoonotic agent is unknown.

View Article and Find Full Text PDF

The zoonotic Plasmodium knowlesi parasite is the most common cause of human malaria in Malaysia. Genetic analysis has shown that the parasites are divided into three subpopulations according to their geographic origin (Peninsular or Borneo) and, in Borneo, their macaque host (Macaca fascicularis or M. nemestrina).

View Article and Find Full Text PDF