Plasmodium Simium and Saimiri Boliviensis as a Model System for Testing Candidate Vaccines Against Plasmodium Vivax

Collins, William E.; Sullivan, JoAnn S.; Galland, G. Gale; Williams, Allison; Nace, Douglas; Williams, Tyrone; Barnwell, John W.

doi:10.4269/ajtmh.2005.73.644

Cited by 8 publications

(5 citation statements)

References 18 publications

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“…The well-established [5,32,62] S. boliviensis vivax malaria model allows isolation of life cycle stage-enriched iRBC, with blood draws after infection timed to allow for the isolation and enrichment of specific stages such as trophozoites. This overcomes difficulties obtaining stage-specific proteomes from human patients harboring asynchronous life cycle stages and/or multiple P. vivax strains when patient samples are pooled.…”

Section: Discussionmentioning

confidence: 99%

“…The combined S. boliviensis iRBC Pv-Proteomes 1 and 2 total of 3209 proteins is substantially larger than the 842 protein human RBC membrane proteome, which itself had overlaps ranging only from 29–53% with other published RBC membrane proteomes [74]. In Pv-Proteomes 1 and 2 we observed 26 of the 34 P. falciparum [32]-ring/early trophozoite stage-predicted 40S ribosomal subunits, and ~35 of 40 predicted 60S subunits, suggesting fairly consistent expression of ribosomal subunits in both species. Ten of the 40S subunits and seven 60S subunits are observed for both P. vivax and S. boliviensis .…”

Section: Discussionmentioning

confidence: 99%

“…Pooling samples from patients will increase parasite yields but results in the increased likelihood (or inevitability) of multiple strains and assorted possible protein modifications in the analyzed samples. An alternative is the use of suitable non-human primate (NHP) experimental models, such as the Bolivian squirrel monkey S. boliviensis [5,32–34]. Using this model, specific P. vivax blood-stage infections can be optimized with adequate blood draws timed for the predominance of distinctive developmental stages; thus increasing the potential of identifying low and high abundance proteins, enabling the association of a greater number of proteins and their putative functions with individual stages of development, and beginning to associate specific protein modifications detected in distinct in vivo biological replicates with disease processes.…”

Section: Introductionmentioning

confidence: 99%

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Plasmodium vivax trophozoite-stage proteomes

Anderson

Lapp

Akinyi

et al. 2015

Journal of Proteomics

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Plasmodium vivax is the causative infectious agent of 80–300 million annual cases of malaria. Many aspects of this parasite’s biology remain unknown. To further elucidate the interaction of P. vivax with its Saimiri boliviensis host, we obtained detailed proteomes of infected red blood cells, representing the trophozoite-enriched stage of development. Data from two of three biological replicate proteomes, emphasized here, were analyzed using five search engines, which enhanced identifications and resulted in the most comprehensive P. vivax proteomes to date, with 1375 P. vivax and 3209 S. boliviensis identified proteins. Ribosome subunit proteins were noted for both P. vivax and S. boliviensis, consistent with P. vivax’s known reticulocyte host–cell specificity. A majority of the host and pathogen proteins identified belong to specific functional categories, and several parasite gene families, while 33% of the P. vivax proteins have no reported function. Hemoglobin was significantly oxidized in both proteomes, and additional protein oxidation and nitration was detected in one of the two proteomes. Detailed analyses of these post-translational modifications are presented. The proteins identified here significantly expand the known P. vivax proteome and complexity of available host protein functionality underlying the host–parasite interactive biology, and reveal unsuspected oxidative modifications that may impact protein function. Biological significance Plasmodium vivax malaria is a serious neglected disease, causing an estimated 80 to 300 million cases annually in 95 countries. Infection can result in significant morbidity and possible death. P. vivax, unlike the much better-studied Plasmodium falciparum species, cannot be grown in long-term culture, has a dormant form in the liver called the hypnozoite stage, has a reticulocyte host–cell preference in the blood, and creates caveolae vesicle complexes at the surface of the infected reticulocyte membranes. Studies of stage-specific P. vivax expressed proteomes have been limited in scope and focused mainly on pathogen proteins, thus limiting understanding of the biology of this pathogen and its host interactions. Here three P. vivax proteomes are reported from biological replicates based on purified trophozoite-infected reticulocytes from different Saimiri boliviensis infections (the main non-human primate experimental model for P. vivax biology and pathogenesis). An in-depth analysis of two of the proteomes using 2D LC/MS/MS and multiple search engines identified 1375 pathogen proteins and 3209 host proteins. Numerous functional categories of both host and pathogen proteins were identified, including several known P. vivax protein family members (e.g., PHIST, eTRAMP and VIR), and 33% of protein identifications were classified as hypothetical. Ribosome subunit proteins were noted for both P. vivax and S. boliviensis, consistent with this parasite species’ known reticulocyte host–cell specificity. In two biological replicates analyzed for post-translational modif...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Plasmodium vivax trophozoite-stage proteomes

Anderson

Lapp

Akinyi

et al. 2015

Journal of Proteomics

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“…Other strains of monkey adapted P. vivax such as Belem and Palo Alto (Vietnam IV) because of consistent and high parasitaemia in non-splenectomized hosts are particularly suited for testing blood-stage vaccines [ 173 ]. P. simium , a natural adaptation of P. vivax in South American howler and spider monkeys can be used in either Saimiri or Aotus species to evaluate either pre-erythrocytic or blood-stage vaccines [ 174 ].…”

Section: Introductionmentioning

confidence: 99%

Plasmodium vivax: who cares?

Galinski

Barnwell

2008

Malar J

134

120

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More attention is being focused on malaria today than any time since the world's last efforts to achieve eradication over 40 years ago. The global community is now discussing strategies aimed at dramatically reducing malarial disease burden and the eventual eradication of all types of malaria, everywhere. As a consequence, Plasmodium vivax, which has long been neglected and mistakenly considered inconsequential, is now entering into the strategic debates taking place on malaria epidemiology and control, drug resistance, pathogenesis and vaccines. Thus, contrary to the past, the malaria research community is becoming more aware and concerned about the widespread spectrum of illness and death caused by up to a couple of hundred million cases of vivax malaria each year. This review brings these issues to light and provides an overview of P. vivax vaccine development, then and now. Progress had been slow, given inherent research challenges and minimal support in the past, but prospects are looking better for making headway in the next few years. P. vivax, known to invade the youngest red blood cells, the reticulocytes, presents a strong challenge towards developing a reliable long-term culture system to facilitate needed research. The P. vivax genome was published recently, and vivax researchers now need to coordinate efforts to discover new vaccine candidates, establish new vaccine approaches, capitalize on non-human primate models for testing, and investigate the unique biological features of P. vivax, including the elusive P. vivax hypnozoites. Comparative studies on both P. falciparum and P. vivax in many areas of research will be essential to eradicate malaria. And to this end, the education and training of future generations of dedicated "malariologists" to advance our knowledge, understanding and the development of new interventions against each of the malaria species infecting humans also will be essential.

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“…Due to its close relationship to P. vivax, P. simium has been proposed as a model to study the efficacy of vaccine candidates (Collins et al 2005). No genome, which could provide valuable information both on its origins and on host adaptations, is currently available.…”

Section: Plasmodium Simiummentioning

confidence: 99%

Non-human primate malaria parasites: out of the forest and into the laboratory

Martinelli

Culleton

2016

Parasitology

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The study of malaria in the laboratory relies on either the in vitro culture of human parasites, or the use of non-human malaria parasites in laboratory animals. In this review, we address the use of non-human primate malaria parasite species (NHPMPs) in laboratory research. We describe the features of the most commonly used NHPMPs, review their contribution to our understanding of malaria to date, and discuss their potential contribution to future studies.

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Plasmodium Simium and Saimiri Boliviensis as a Model System for Testing Candidate Vaccines Against Plasmodium Vivax

Cited by 8 publications

References 18 publications

Plasmodium vivax trophozoite-stage proteomes

Plasmodium vivax trophozoite-stage proteomes

Plasmodium vivax: who cares?

Non-human primate malaria parasites: out of the forest and into the laboratory

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