7 results on '"Fyfe AJ"'
Search Results
2. Functional Characterization and Comparison of Plasmodium falciparum Proteins as Targets of Transmission-blocking Antibodies.
- Author
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Nikolaeva D, Illingworth JJ, Miura K, Alanine DGW, Brian IJ, Li Y, Fyfe AJ, Da DF, Cohuet A, Long CA, Draper SJ, and Biswas S
- Subjects
- Adult, Animals, Anopheles parasitology, Epitopes immunology, Female, HEK293 Cells, Humans, Immunoglobulin G immunology, Malaria Vaccines immunology, Malaria, Falciparum epidemiology, Malaria, Falciparum virology, Male, Mali epidemiology, Mice, Mice, Inbred BALB C, Mosquito Vectors parasitology, Phosphopyruvate Hydratase immunology, Proteome, Proteomics methods, Vaccination, Antibodies, Blocking immunology, Malaria, Falciparum immunology, Malaria, Falciparum transmission, Plasmodium falciparum immunology, Protozoan Proteins immunology, Recombinant Proteins immunology
- Abstract
Plasmodium falciparum malaria continues to evade control efforts, utilizing highly specialized sexual-stages to transmit infection between the human host and mosquito vector. In a vaccination model, antibodies directed to sexual-stage antigens, when ingested in the mosquito blood meal, can inhibit parasite growth in the midgut and consequently arrest transmission. Despite multiple datasets for the Plasmodium sexual-stage transcriptome and proteome, there have been no rational screens to identify candidate antigens for transmission-blocking vaccine (TBV) development. This study characterizes 12 proteins from across the P. falciparum sexual-stages as possible TBV targets. Recombinant proteins are heterologously expressed as full-length ectodomains in a mammalian HEK293 cell system. The proteins recapitulate native parasite epitopes as assessed by indirect fluorescence assay and a proportion exhibits immunoreactivity when tested against sera from individuals living in malaria-endemic Burkina Faso and Mali. Purified IgG generated to the mosquito-stage parasite antigen enolase demonstrates moderate inhibition of parasite development in the mosquito midgut by the ex vivo standard membrane feeding assay. The findings support the use of rational screens and comparative functional assessments in identifying proteins of the P. falciparum transmission pathway and establishing a robust pre-clinical TBV pipeline., (© 2020 Nikolaeva et al.)
- Published
- 2020
- Full Text
- View/download PDF
3. Role of Activins in Hepcidin Regulation during Malaria.
- Author
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Spottiswoode N, Armitage AE, Williams AR, Fyfe AJ, Biswas S, Hodgson SH, Llewellyn D, Choudhary P, Draper SJ, Duffy PE, and Drakesmith H
- Subjects
- Animals, Disease Models, Animal, Gene Expression Regulation, Humans, Mice, Activins metabolism, Hepcidins metabolism, Malaria pathology, Plasmodium berghei growth & development, Plasmodium chabaudi growth & development
- Abstract
Epidemiological observations have linked increased host iron with malaria susceptibility, and perturbed iron handling has been hypothesized to contribute to the potentially life-threatening anemia that may accompany blood-stage malaria infection. To improve our understanding of these relationships, we examined the pathways involved in regulation of the master controller of iron metabolism, the hormone hepcidin, in malaria infection. We show that hepcidin upregulation in Plasmodium berghei murine malaria infection was accompanied by changes in expression of bone morphogenetic protein (BMP)/sons of mothers against decapentaplegic (SMAD) pathway target genes, a key pathway involved in hepcidin regulation. We therefore investigated known agonists of the BMP/SMAD pathway and found that Bmp gene expression was not increased in infection. In contrast, activin B, which can signal through the BMP/SMAD pathway and has been associated with increased hepcidin during inflammation, was upregulated in the livers of Plasmodium berghei -infected mice; hepatic activin B was also upregulated at peak parasitemia during infection with Plasmodium chabaudi Concentrations of the closely related protein activin A increased in parallel with hepcidin in serum from malaria-naive volunteers infected in controlled human malaria infection (CHMI) clinical trials. However, antibody-mediated neutralization of activin activity during murine malaria infection did not affect hepcidin expression, suggesting that these proteins do not stimulate hepcidin upregulation directly. In conclusion, we present evidence that the BMP/SMAD signaling pathway is perturbed in malaria infection but that activins, although raised in malaria infection, may not have a critical role in hepcidin upregulation in this setting., (Copyright © 2017 Spottiswoode et al.)
- Published
- 2017
- Full Text
- View/download PDF
4. Enhancing immunogenicity and transmission-blocking activity of malaria vaccines by fusing Pfs25 to IMX313 multimerization technology.
- Author
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Li Y, Leneghan DB, Miura K, Nikolaeva D, Brian IJ, Dicks MD, Fyfe AJ, Zakutansky SE, de Cassan S, Long CA, Draper SJ, Hill AV, Hill F, and Biswas S
- Subjects
- Adenoviridae genetics, Adenoviridae immunology, Adjuvants, Immunologic administration & dosage, Adjuvants, Immunologic chemistry, Animals, Antigens, Protozoan genetics, Antigens, Protozoan immunology, Culicidae drug effects, Culicidae parasitology, Gene Expression, Genetic Vectors chemistry, Genetic Vectors immunology, Germinal Center drug effects, Germinal Center immunology, Humans, Insect Vectors drug effects, Insect Vectors parasitology, Life Cycle Stages drug effects, Life Cycle Stages immunology, Malaria Vaccines administration & dosage, Malaria Vaccines genetics, Malaria, Falciparum immunology, Malaria, Falciparum parasitology, Mice, Mice, Inbred BALB C, Pichia genetics, Pichia metabolism, Plasmids chemistry, Plasmids immunology, Plasmodium falciparum growth & development, Plasmodium falciparum immunology, Protozoan Proteins administration & dosage, Protozoan Proteins genetics, Recombinant Fusion Proteins administration & dosage, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins immunology, Vaccination, Vaccines, Synthetic, Adjuvants, Immunologic genetics, Antibodies, Protozoan biosynthesis, Immunogenicity, Vaccine, Malaria Vaccines immunology, Malaria, Falciparum prevention & control, Plasmodium falciparum drug effects, Protozoan Proteins immunology
- Abstract
Transmission-blocking vaccines (TBV) target the sexual-stages of the malaria parasite in the mosquito midgut and are widely considered to be an essential tool for malaria elimination. High-titer functional antibodies are required against target antigens to achieve effective transmission-blocking activity. We have fused Pfs25, the leading malaria TBV candidate antigen to IMX313, a molecular adjuvant and expressed it both in ChAd63 and MVA viral vectors and as a secreted protein-nanoparticle. Pfs25-IMX313 expressed from viral vectors or as a protein-nanoparticle is significantly more immunogenic and gives significantly better transmission-reducing activity than monomeric Pfs25. In addition, we demonstrate that the Pfs25-IMX313 protein-nanoparticle leads to a qualitatively improved antibody response in comparison to soluble Pfs25, as well as to significantly higher germinal centre (GC) responses. These results demonstrate that antigen multimerization using IMX313 is a very promising strategy to enhance antibody responses against Pfs25, and that Pfs25-IMX313 is a highly promising TBV candidate vaccine.
- Published
- 2016
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5. Successful routine cytogenetic analysis from trephine biopsy specimens following failure to aspirate bone marrow.
- Author
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Fyfe AJ, Drummond M, and Morris A
- Subjects
- Adult, Cytogenetic Analysis, Female, Humans, Male, Middle Aged, Neoplasms genetics, Bone Marrow Examination methods, Neoplasms diagnosis
- Published
- 2009
- Full Text
- View/download PDF
6. Multiple splenic calcifications.
- Author
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Fyfe AJ and Gallipoli P
- Subjects
- Aged, Calcinosis complications, Humans, Liver diagnostic imaging, Liver Diseases complications, Liver Diseases diagnostic imaging, Lung Neoplasms complications, Lung Neoplasms diagnostic imaging, Lymphoma, Large B-Cell, Diffuse complications, Lymphoma, Large B-Cell, Diffuse diagnostic imaging, Male, Splenic Diseases complications, Tomography, X-Ray Computed, Calcinosis diagnostic imaging, Spleen diagnostic imaging, Splenic Diseases diagnostic imaging
- Published
- 2009
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7. Multiple Pappenheimer bodies.
- Author
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Fyfe AJ and Soutar RL
- Subjects
- Antitubercular Agents adverse effects, Emergencies, Folic Acid Deficiency complications, Humans, Isoniazid adverse effects, Male, Middle Aged, Splenectomy, Staining and Labeling, Tuberculosis drug therapy, Alcoholism blood, Erythrocyte Inclusions pathology, Siderosis blood
- Published
- 2005
- Full Text
- View/download PDF
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