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Kevin Marsh - One of the best experts on this subject based on the ideXlab platform.
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kinetics of antibody responses to plasmodium falciparum infected erythrocyte variant Surface Antigens
The Journal of Infectious Diseases, 2003Co-Authors: Samson M Kinyanjui, Peter C Bull, Kevin Marsh, C I NewboldAbstract:The kinetics of antibody responses to the Plasmodium falciparum malaria parasite-induced erythrocyte Surface Antigens (PIESAs) in 26 Kenyan children were examined by use of flow cytometry and agglutination assays. Although 19 of the 26 children mounted a primary antibody response to PIESAs within 2 weeks of experiencing an acute episode and maintained high antibody levels for at least 12 weeks, the remaining 7 children had responses that were weak and brief. Resistance to reparasitization was decreased in the children with short-lived responses. Isotype profiles of responses in 11 of the children studied suggest that they may have failed to switch to IgG after the initial IgM response. These data suggest that children vary widely in their ability to respond to PIESAs and that, in some individuals or with certain PIESA variants, short-lived antibody responses are induced that may be associated with poor antibody class switching.
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the role of antibodies to plasmodium falciparum infected erythrocyte Surface Antigens in naturally acquired immunity to malaria
Trends in Microbiology, 2002Co-Authors: Peter C Bull, Kevin MarshAbstract:Plasmodium falciparum, the most virulent species of human malaria parasite, causes 1-3 million deaths per year. Because this parasite is susceptible to naturally acquired host immunity the main burden of diseases falls on young children. The mechanism of this immunity is still unclear. However, the parasite makes a considerable investment in the insertion of highly polymorphic Antigens (parasite-infected-erythrocyte Surface Antigens, PIESA) on the infected erythrocyte Surface, and these Antigens are potentially important immune targets.
Colin J Sutherland - One of the best experts on this subject based on the ideXlab platform.
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antibody responses to Surface Antigens of plasmodium falciparum gametocyte infected erythrocytes and their relation to gametocytaemia
BMJ Global Health, 2017Co-Authors: Bismarck Dinko, Elizabeth C King, Geoffrey A T Targett, Colin J SutherlandAbstract:Background An essential element for continuing transmission of Plasmodium falciparum is the availability of mature gametocytes in human peripheral circulation for uptake by mosquitoes. Natural immune responses to circulating gametocytes may play a role in reducing transmission from humans to mosquitoes. Methods Here, antibody recognition of the Surface of mature intra-erythrocytic gametocytes produced either by a laboratory-adapted parasite, 3D7, or by a recent clinical isolate of Kenyan origin (HL1204), was evaluated longitudinally in a cohort of Ghanaian school children by flow cytometry. Results This showed that a proportion of children exhibited antibody responses that recognised gametocyte Surface Antigens on one or both parasite lines. A subset of the children maintained detectable anti-gametocyte Surface antigen (GSA) antibody levels during the five week study period. There was indicative evidence that children with anti-GSA antibodies present at enrolment were less likely to have patent gametocytaemia at subsequent visits (OR=0.29, 95% CI: 0.06–1.05; p=0.034). Conclusions Our data support the existence of Antigens on the Surface of gametocyte – infected erythrocytes, but further studies are needed to confirm whether antibodies against them reduce gametocyte carriage. The identification of GSA would allow their evaluation as potential anti-gametocyte vaccine candidates and/or biomarkers for gametocyte carriage.
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antibody responses to Surface Antigens of plasmodium falciparum gametocyte infected erythrocytes and their relation to gametocytaemia
Parasite Immunology, 2016Co-Authors: Bismarck Dinko, Elizabeth C King, Geoffrey A T Targett, Colin J SutherlandAbstract:: An essential element for continuing transmission of Plasmodium falciparum is the availability of mature gametocytes in human peripheral circulation for uptake by mosquitoes. Natural immune responses to circulating gametocytes may play a role in reducing transmission from humans to mosquitoes. Here, antibody recognition of the Surface of mature intra-erythrocytic gametocytes produced either by a laboratory-adapted parasite, 3D7, or by a recent clinical isolate of Kenyan origin (HL1204), was evaluated longitudinally in a cohort of Ghanaian school children by flow cytometry. This showed that a proportion of children exhibited antibody responses that recognized gametocyte Surface Antigens on one or both parasite lines. A subset of the children maintained detectable anti-gametocyte Surface antigen (GSA) antibody levels during the 5 week study period. There was indicative evidence that children with anti-GSA antibodies present at enrolment were less likely to have patent gametocytaemia at subsequent visits (odds ratio = 0·29, 95% CI 0·06-1·05; P = 0·034). Our data support the existence of Antigens on the Surface of gametocyte-infected erythrocytes, but further studies are needed to confirm whether antibodies against them reduce gametocyte carriage. The identification of GSA would allow their evaluation as potential anti-gametocyte vaccine candidates and/or biomarkers for gametocyte carriage.
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Surface Antigens of plasmodium falciparum gametocytes a new class of transmission blocking vaccine targets
Molecular and Biochemical Parasitology, 2009Co-Authors: Colin J SutherlandAbstract:The re-establishment of elimination and eradication on the malaria control agenda has led to calls for renewed effort in the development of parasite transmission-blocking interventions. Vaccines are ideally suited to this task, but progress towards an anti-gamete transmission-blocking vaccine, designed to act on parasites in blood-fed mosquitoes, has been slow. Recent work has confirmed that the Surface of the gametocyte-infected erythrocyte presents Antigens to the host immune system, and elicits specific humoral immune responses to these Antigens, termed gametocyte Surface Antigens (GSAs). Likely candidate molecules, including Antigens encoded by sub-telomeric multi-gene families, are discussed, and a hypothetical group of parasite molecules involved in spatial and temporal signal transduction in the human host is proposed, the tropins and circadins. The next steps for development of anti-gametocyte transmission-blocking vaccines for P. falciparum and the other human malaria species are considered.
Adrian J F Luty - One of the best experts on this subject based on the ideXlab platform.
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ANTIBODIES TO RIFIN: A COMPONENT OF NATURALLY ACQUIRED RESPONSES TO PLASMODIUM FALCIPARUM VARIANT Surface Antigens ON INFECTED ERYTHROCYTES
2015Co-Authors: Mohamed S. Abdel-latif, Gerardo Cabrera, Adrian J F LutyAbstract:Abstract. We used a pool of recombinant rifin proteins to pre-adsorb antibodies to rifin in the plasma of semi-immune African (Gabonese) adults and showed that this results in a reduction in the level of IgG antibody reactivity to variant Surface Antigens (VSA) measured in a standardized flow cytometric assay with a panel of heterologous parasite isolates. The same methods demonstrated a similar but less-marked contribution of antibodies to the duffy binding-like 1 (DBL-1) domain to the overall anti-VSA response. Thus, we conclude that both antibodies to rifin and, to a lesser extent, antibodies directed to conserved regions of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) DBL-1 domain contribute to the overall antibody response to VSA. We also assessed the associations between these different antibody responses in a cohort of Gabonese children. We found marked differences related to the childrens ’ history of presentation with either mild or severe malaria, but no consistent pattern that would indicate a specific role or influence of antibody responses to rifin
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the sickle cell trait is associated with enhanced immunoglobulin g antibody responses to plasmodium falciparum variant Surface Antigens
The Journal of Infectious Diseases, 2005Co-Authors: Gerardo Cabrera, Florence Migotnabias, Peter G Kremsner, Philippe Deloron, Adrian J F LutyAbstract:The sickle cell trait (HbAS) protects against severe Plasmodium falciparum malaria in young African children. We investigated the extent of the association between HbAS and antibodies directed to parasite-derived variant Surface Antigens (VSAs) on the membrane of infected erythrocytes. We measured immunoglobulin G (IgG) responses with specificity for VSAs of 2 heterologous parasite isolates in 458 Gabonese children aged between 6 months and 11 years. Logistic regression analyses showed a highly significant independent association (P<.001) between carriage of HbAS and the presence of IgG anti-VSA responses; this association was related specifically to IgG1 and IgG4 subclasses in the anti-VSA profile. IgG2 and IgG3 anti-VSA responses were both independently associated with older age, consistent with the pattern observed in semi-immune adults. The results imply that enhanced levels of cross-reactive anti-VSA responses in children with HbAS may be intimately associated with the protection they have against malaria.
Peter C Bull - One of the best experts on this subject based on the ideXlab platform.
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induction of strain transcending antibodies against group a pfemp1 Surface Antigens from virulent malaria parasites
PLOS Pathogens, 2012Co-Authors: Ashfaq Ghumra, Peter C Bull, Jeanphilippe Semblat, Ricardo Ataide, Carolyne Kifude, Yvonne Adams, Antoine Claessens, Damian Nota Anong, Clare FennellAbstract:Sequence diversity in pathogen Antigens is an obstacle to the development of interventions against many infectious diseases. In malaria caused by Plasmodium falciparum, the PfEMP1 family of variant Surface Antigens encoded by var genes are adhesion molecules that play a pivotal role in malaria pathogenesis and clinical disease. PfEMP1 is a major target of protective immunity, however, development of drugs or vaccines based on PfEMP1 is problematic due to extensive sequence diversity within the PfEMP1 family. Here we identified the PfEMP1 variants transcribed by P. falciparum strains selected for a virulence-associated adhesion phenotype (IgM-positive rosetting). The parasites transcribed a subset of Group A PfEMP1 variants characterised by an unusual PfEMP1 architecture and a distinct N-terminal domain (either DBLα1.5 or DBLα1.8 type). Antibodies raised in rabbits against the N-terminal domains showed functional activity (Surface reactivity with live infected erythrocytes (IEs), rosette inhibition and induction of phagocytosis of IEs) down to low concentrations (<10 µg/ml of total IgG) against homologous parasites. Furthermore, the antibodies showed broad cross-reactivity against heterologous parasite strains with the same rosetting phenotype, including clinical isolates from four sub-Saharan African countries that showed Surface reactivity with either DBLα1.5 antibodies (variant HB3var6) or DBLα1.8 antibodies (variant TM284var1). These data show that parasites with a virulence-associated adhesion phenotype share IE Surface epitopes that can be targeted by strain-transcending antibodies to PfEMP1. The existence of shared Surface epitopes amongst functionally similar disease-associated P. falciparum parasite isolates suggests that development of therapeutic interventions to prevent severe malaria is a realistic goal.
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kinetics of antibody responses to plasmodium falciparum infected erythrocyte variant Surface Antigens
The Journal of Infectious Diseases, 2003Co-Authors: Samson M Kinyanjui, Peter C Bull, Kevin Marsh, C I NewboldAbstract:The kinetics of antibody responses to the Plasmodium falciparum malaria parasite-induced erythrocyte Surface Antigens (PIESAs) in 26 Kenyan children were examined by use of flow cytometry and agglutination assays. Although 19 of the 26 children mounted a primary antibody response to PIESAs within 2 weeks of experiencing an acute episode and maintained high antibody levels for at least 12 weeks, the remaining 7 children had responses that were weak and brief. Resistance to reparasitization was decreased in the children with short-lived responses. Isotype profiles of responses in 11 of the children studied suggest that they may have failed to switch to IgG after the initial IgM response. These data suggest that children vary widely in their ability to respond to PIESAs and that, in some individuals or with certain PIESA variants, short-lived antibody responses are induced that may be associated with poor antibody class switching.
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the role of antibodies to plasmodium falciparum infected erythrocyte Surface Antigens in naturally acquired immunity to malaria
Trends in Microbiology, 2002Co-Authors: Peter C Bull, Kevin MarshAbstract:Plasmodium falciparum, the most virulent species of human malaria parasite, causes 1-3 million deaths per year. Because this parasite is susceptible to naturally acquired host immunity the main burden of diseases falls on young children. The mechanism of this immunity is still unclear. However, the parasite makes a considerable investment in the insertion of highly polymorphic Antigens (parasite-infected-erythrocyte Surface Antigens, PIESA) on the infected erythrocyte Surface, and these Antigens are potentially important immune targets.
Daniel K Howe - One of the best experts on this subject based on the ideXlab platform.
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Enzyme-Linked Immunosorbent Assays for Detection of Equine Antibodies Specific to Sarcocystis neurona Surface Antigens
Clinical and Vaccine Immunology, 2005Co-Authors: Jessica S Hoane, Jennifer K Morrow, William J. Saville, David E. Granstrom, Daniel K HoweAbstract:Sarcocystis neurona is the primary causative agent of equine protozoal myeloencephalitis (EPM), a common neurologic disease of horses in the Americas. We have developed a set of enzyme-linked immunosorbent assays (ELISAs) based on the four major Surface Antigens of S. neurona (SnSAGs) to analyze the equine antibody response to S. neurona. The SnSAG ELISAs were optimized and standardized with a sample set of 36 equine sera that had been characterized by Western blotting against total S. neurona parasite antigen, the current gold standard for S. neurona serology. The recombinant SnSAG2 (rSnSAG2) ELISA showed the highest sensitivity and specificity at 95.5% and 92.9%, respectively. In contrast, only 68.2% sensitivity and 71.4% specificity were achieved with the rSnSAG1 ELISA, indicating that this antigen may not be a reliable serological marker for analyzing antibodies against S. neurona in horses. Importantly, the ELISA Antigens did not show cross-reactivity with antisera to Sarcocystis fayeri or Neospora hughesi, two other equine parasites. The accuracy and reliability exhibited by the SnSAG ELISAs suggest that these assays will be valuable tools for examining the equine immune response against S. neurona infection, which may help in understanding the pathobiology of this accidental parasite-host interaction. Moreover, with modification and further investigation, the SnSAG ELISAs have potential for use as immunodiagnostic tests to aid in the identification of horses affected by EPM.
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sarcocystis neurona merozoites express a family of immunogenic Surface Antigens that are orthologues of the toxoplasma gondii Surface Antigens sags and sag related sequences
Infection and Immunity, 2005Co-Authors: Daniel K Howe, Rajshekhar Y Gaji, Meaghan Mrozbarrett, Marcjan Gubbels, Boris Striepen, S StamperAbstract:Sarcocystis neurona is a member of the Apicomplexa that causes myelitis and encephalitis in horses but normally cycles between the opossum and small mammals. Analysis of an S. neurona expressed sequence tag (EST) database revealed four paralogous proteins that exhibit clear homology to the family of Surface Antigens (SAGs) and SAG-related sequences of Toxoplasma gondii. The primary peptide sequences of the S. neurona proteins are consistent with the two-domain structure that has been described for the T. gondii SAGs, and each was predicted to have an amino-terminal signal peptide and a carboxyl-terminal glycolipid anchor addition site, suggesting Surface localization. All four proteins were confirmed to be membrane associated and displayed on the Surface of S. neurona merozoites. Due to their Surface localization and homology to T. gondii Surface Antigens, these S. neurona proteins were designated SnSAG1, SnSAG2, SnSAG3, and SnSAG4. Consistent with their homology, the SnSAGs elicited a robust immune response in infected and immunized animals, and their conserved structure further suggests that the SnSAGs similarly serve as adhesins for attachment to host cells. Whether the S. neurona SAG family is as extensive as the T. gondii SAG family remains unresolved, but it is probable that additional SnSAGs will be revealed as more S. neurona ESTs are generated. The existence of an SnSAG family in S. neurona indicates that expression of multiple related Surface Antigens is not unique to the ubiquitous organism T. gondii. Instead, the SAG gene family is a common trait that presumably has an essential, conserved function(s).
