Partial protection against P. vivax infection diminishes hypnozoite burden and blood-stage relapses

Schäfer, Carola; Dambrauskas, Nicholas; Reynolds, Laura M.; Trakhimets, Olesya; Raappana, Andrew; Flannery, Erika L.; Roobsoong, Wanlapa; Sattabongkot, Jetsumon; Mikolajczak, Sebastian A.; Kappe, Stefan H. I.; Sather, D. Noah

doi:10.1016/j.chom.2021.03.011

Cited by 20 publications

(20 citation statements)

References 19 publications

(15 reference statements)

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“…Several factors such as difficulties in culture, limited animal models for P. vivax , other technical challenges including protein function, antigenic diversity, and inhibition of growth in laboratory conditions prevent the selection of suitable antigens for P. vivax studies [ 17 ]. Researchers have recognized that the central repeat regions of the CSP in P. vivax are epitopes of B cells, and specific antibodies to this region can protect a person against malaria by blocking the attack of sporozoites to the liver cells [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Serological responses to a soluble recombinant circumsporozoite protein-VK210 of Plasmodium vivax (rPvCSP-VK210) among Iranian malaria patients

et al. 2021

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Background Circumsporozoite protein (CSP) has a central immune domain that includes short regions of repeating amino acid sequences. This immunodynamic region is an epitope of B cells that can elicit an immune response in human and laboratory animals. The aim of the present study was to express the recombinant PvCSP-VK210 antigen and evaluate it for assaying antibodies obtained during human P. vivax infection by Western blotting and indirect ELISA (enzyme-linked immunosorbent assay). Method Genomic DNA of P. vivax was isolated from a blood sample of an Iranian person with vivax malaria, and by PCR, the fragment of the PvCSP-VK210 gene was amplified. The gene fragment was cut after gel purification by BamHI and HindIII enzymes and then cloned into pET28a expression vector. Finally, the recombinant pET28a was transformed into the E.coli BL21 (DE3) as the expression host. In order to produce His-tagged protein, the expression host was cultured in LB medium. The protein was purified by Ni–NTA columns and immobilized metal affinity chromatography, and after confirmation by Western blotting technique, was used as the antigen in the indirect ELISA test. Results The recombinant protein was expressed and purified as a 32-kDa protein. The sensitivity and specificity of the indirect ELISA test with the recombinant PvCSP-VK210 antigen were 61.42% and 97.14%, respectively, based on OD = 0.313. Between the results of the microscopic test and the indirect ELISA test with the recombinant PvCSP-VK210 antigen there was a Kappa coefficient of 0.586. The positive and negative predictive value and validity of the ELISA test with the recombinant PvCSP-VK210 antigen were 95.55%, 71.57%, 79.28%, respectively. Conclusion The sensitivity of the indirect ELISA method with the recombinant PvCSP-VK210 antigen was 61.42%, which is the first report from Iran.

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Section: Discussionmentioning

confidence: 99%

Serological responses to a soluble recombinant circumsporozoite protein-VK210 of Plasmodium vivax (rPvCSP-VK210) among Iranian malaria patients

et al. 2021

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“…Such a high level of parasitaemia is rarely seen in human infections or carefully monitored and controlled NHP infections. Moreover, relapse biology and associated immune responses currently cannot be studied using rodent malarial infection models (particularly given the lack of relapses in rodents, except in humanized mice [ 472 , 473 ]), and as discussed above research on relapses is formidable with humans [ 231 – 233 ], making the NHP models for studying relapses preferable if not essential.…”

Section: Malaria Research Advances With Systems Approaches and Nonhum...mentioning

confidence: 99%

Systems biology of malaria explored with nonhuman primates

Galinski

2022

Malar J

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Abstract“The Primate Malarias” book has been a uniquely important resource for multiple generations of scientists, since its debut in 1971, and remains pertinent to the present day. Indeed, nonhuman primates (NHPs) have been instrumental for major breakthroughs in basic and pre-clinical research on malaria for over 50 years. Research involving NHPs have provided critical insights and data that have been essential for malaria research on many parasite species, drugs, vaccines, pathogenesis, and transmission, leading to improved clinical care and advancing research goals for malaria control, elimination, and eradication. Whilst most malaria scientists over the decades have been studying Plasmodium falciparum, with NHP infections, in clinical studies with humans, or using in vitro culture or rodent model systems, others have been dedicated to advancing research on Plasmodium vivax, as well as on phylogenetically related simian species, including Plasmodium cynomolgi, Plasmodium coatneyi, and Plasmodium knowlesi. In-depth study of these four phylogenetically related species over the years has spawned the design of NHP longitudinal infection strategies for gathering information about ongoing infections, which can be related to human infections. These Plasmodium-NHP infection model systems are reviewed here, with emphasis on modern systems biological approaches to studying longitudinal infections, pathogenesis, immunity, and vaccines. Recent discoveries capitalizing on NHP longitudinal infections include an advanced understanding of chronic infections, relapses, anaemia, and immune memory. With quickly emerging new technological advances, more in-depth research and mechanistic discoveries can be anticipated on these and additional critical topics, including hypnozoite biology, antigenic variation, gametocyte transmission, bone marrow dysfunction, and loss of uninfected RBCs. New strategies and insights published by the Malaria Host–Pathogen Interaction Center (MaHPIC) are recapped here along with a vision that stresses the importance of educating future experts well trained in utilizing NHP infection model systems for the pursuit of innovative, effective interventions against malaria.

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“…Thus, the model can be used for studying the liver stage-to-blood stage transition of P. vivax ( Mikolajczak et al., 2015 ). The model has also been used to test the efficacy of a pre-erythrocytic vaccine against P. vivax by passive immunization of anti-PvCSP antibodies prior to sporozoite injection, demonstrating that the vaccine could be of high benefit by reducing the hypnozoite reservoir and thereby reducing the number of relapses ( Schafer et al., 2021 ).…”

Section: Humanized Mouse Modelsmentioning

confidence: 99%

Advancing Key Gaps in the Knowledge of Plasmodium vivax Cryptic Infections Using Humanized Mouse Models and Organs-on-Chips

Aparici-Herraiz

Caires

Castillo-Fernandez

et al. 2022

Front. Cell. Infect. Microbiol.

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Plasmodium vivax is the most widely distributed human malaria parasite representing 36.3% of disease burden in the South-East Asia region and the most predominant species in the region of the Americas. Recent estimates indicate that 3.3 billion of people are under risk of infection with circa 7 million clinical cases reported each year. This burden is certainly underestimated as the vast majority of chronic infections are asymptomatic. For centuries, it has been widely accepted that the only source of cryptic parasites is the liver dormant stages known as hypnozoites. However, recent evidence indicates that niches outside the liver, in particular in the spleen and the bone marrow, can represent a major source of cryptic chronic erythrocytic infections. The origin of such chronic infections is highly controversial as many key knowledge gaps remain unanswered. Yet, as parasites in these niches seem to be sheltered from immune response and antimalarial drugs, research on this area should be reinforced if elimination of malaria is to be achieved. Due to ethical and technical considerations, working with the liver, bone marrow and spleen from natural infections is very difficult. Recent advances in the development of humanized mouse models and organs-on-a-chip models, offer novel technological frontiers to study human diseases, vaccine validation and drug discovery. Here, we review current data of these frontier technologies in malaria, highlighting major challenges ahead to study P. vivax cryptic niches, which perpetuate transmission and burden.

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Partial protection against P. vivax infection diminishes hypnozoite burden and blood-stage relapses

Cited by 20 publications

References 19 publications

Serological responses to a soluble recombinant circumsporozoite protein-VK210 of Plasmodium vivax (rPvCSP-VK210) among Iranian malaria patients

Serological responses to a soluble recombinant circumsporozoite protein-VK210 of Plasmodium vivax (rPvCSP-VK210) among Iranian malaria patients

Systems biology of malaria explored with nonhuman primates

Advancing Key Gaps in the Knowledge of Plasmodium vivax Cryptic Infections Using Humanized Mouse Models and Organs-on-Chips

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