Rapid antigen diversification through mitotic recombination in the human malaria parasite Plasmodium falciparum

by Xu Zhang, Noah Alexander, Irina Leonardi, Christopher Mason, Laura A. Kirkman, Kirk W. Deitsch Malaria parasites possess the remarkable ability to maintain chronic infections that fail to elicit a protective immune response, characteristics that have stymied vaccine development and cause people living in endemic regions to remain at risk of malaria despite previous exposure to the disease. These traits stem from the tremendous antigenic diversity displayed by parasites circulating in the field. ForPlasmodium falciparum, the most virulent of the human malaria parasites, this diversity is exemplified by the variant gene family calledvar, which encodes the major surface antigen displayed on infected red blood cells (RBCs). This gene family exhibits virtually limitless diversity whenvar gene repertoires from different parasite isolates are compared. Previous studies indicated that this remarkable genome plasticity results from extensive ectopic recombination betweenvar genes during mitotic replication; however, the molecular mechanisms that direct this process to antigen-encoding loci while the rest of the genome remains relatively stable were not determined. Using targeted DNA double-strand breaks (DSBs) and long-read whole-genome sequencing, we show that a single break within an antigen-encoding region of the genome can result in a cascade of recombination events leading to the generation of multiple chimericvar genes, a process that can greatly accelerate the generation of...
Source: PLoS Biology: Archived Table of Contents - Category: Biology Authors: Source Type: research

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Clinical manifestation of malaria is mainly due to intra-erythrocytic development of Plasmodium parasites. Plasmodium falciparum merozoites, the invasive form of the blood-stage parasite, invade human erythrocytes in a complex but rapid process. This multi-step progression involves interactions between parasite and human host proteins. Here we show that antibodies against a vaccine antigen, PfGAMA, co-immunoprecipitate with PfMSP10. This interaction was validated as direct by surface plasmon resonance analysis. We then demonstrate that antibodies against PfMSP10 have growth inhibitory activity against cultured parasites, w...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Abstract Plasmodium vivax, the chronic relapsing human malaria parasite with the most widespread distribution, possesses proteins associated with the merozoite surface that could be targets for host immune responses and potential vaccine candidates. Of these, the merozoite surface protein 3 of P. vivax (PvMSP3) is an attractive vaccine target as well as a genetic marker for epidemiological surveillance. PvMSP3 comprises a group of protein members encoded by a multigene family. Although some protein members, i.e. PvMSP3α and PvMSP3β, have been targets for molecular and immunological investigations, the m...
Source: Infection, Genetics and Evolution - Category: Genetics & Stem Cells Authors: Tags: Infect Genet Evol Source Type: research
In this study, using samples collected from young children in Ghana at multiple time points during a longitudinal study, we adapted a predictive modelling framework which combines feature selection and machine learning techniques to identify an antigen signature of clinical immunity to malaria. Our results show that an individual's immune status can be accurately predicted by measuring antibody responses to a small defined set of 15 target antigens. We further demonstrate that the identified immune signature is highly versatile and capable of providing precise and accurate estimates of clinical protection from malaria in a...
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Tags: Mol Cell Proteomics Source Type: research
Conclusions: Naturally acquired sexual stage immunity, as detected by antibodies to Pfs230 and Pfs48/45, was present in most studies analyzed. Significant between-study heterogeneity was seen, and methodological factors were a major contributor to this, and prevented further analysis of epidemiological and biological factors. This demonstrates a need for standardized protocols for conducting and reporting seroepidemiological analyses.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In conclusion, the overall results present the molecular characterization of annexin B30, annexin B5a, annexin B7a and annexin B5b from S. mansoni in host-parasite interactions and strongly suggest that the molecules could be useful candidates for vaccine or diagnostic development.
Source: Molecular and Biochemical Parasitology - Category: Parasitology Source Type: research
Publication date: Available online 12 June 2019Source: Parasitology InternationalAuthor(s): Vipin Kumar Deo, Yu Inagaki, Elsa Herdiana Murhandarwati, Widya Asmara, Takatsugu Miyazaki, Tatsuya Kato, Enoch Y. ParkAbstractPlasmodium falciparum is a blood protozoan parasite, transmitted by Anopheles mosquitoes vectors, that can cause morbidity and even leads to mortality in tropical countries. Strategies are directed to combat malaria including development of diagnostic tools, serological markers and vaccinations. A target under intensive studies is Merozoite Surface Protein (MSP)-3. The aim of this study is to express and pur...
Source: Parasitology International - Category: Parasitology Source Type: research
This study was carried out in accordance with the recommendations of Institutional Review Board of the Federal University of Bahia, Brazil, with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the Institutional Review Board of the Federal University of Bahia, Brazil (approval number 693.111). Human Blood Samples and Preparation of Peripheral Blood Cells Peripheral blood mononuclear cells (PBMC) were separated from heparinized venous blood by Ficoll-Hypaque gradient centrifugation. Cells were then washed in ...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
This study including human samples was carried out in accordance with the recommendations of the ICH/GCP guidelines, Comité de Etica para Investigación con Humanos, Centro Internacional de Vacunas (CECIV, Cali, Colombia), and the protocol approved by the CECIV. All subjects gave written informed consent in accordance with the Declaration of Helsinki. All animal protocols that include experimental animal procedures using mice and NHP were carried out in accordance with the US Animal Welfare Act and approved by the Emory University's Institutional Animal Care and Use Committee and followed accordingly....
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
Sean P. Saunders1, Erica G. M. Ma1,2, Carlos J. Aranda1 and Maria A. Curotto de Lafaille1,3* 1Division of Pulmonary, Critical Care and Sleep Medicine, Laboratory of Allergy and Inflammation, Department of Medicine, New York University, New York, NY, United States 2Sackler Institute of Graduate Biomedical Sciences, New York University, New York, NY, United States 3Department of Cell Biology, New York University School of Medicine, New York, NY, United States The long-term effectiveness of antibody responses relies on the development of humoral immune memory. Humoral immunity is maintained by long-lived plasma ce...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
This study was performed in accordance with the ethical standards of the Institutional Animal Care and Use Committee (IACUC, approval FUA-007-14) from the Unidad de Biología Comparativa (UBA) at Pontificia Universidad Javeriana (PUJ, Bogotá, Colombia). All animal studies were conducted in accordance with the “Guide for the Care and Use of Laboratory Animals” from UBA-PUJ. The present study was described according to the Animal Research: Reporting in vivo Experiments (ARRIVE) criteria from the National Center for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) (32). Mice ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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