Article
Microbiology
Brittany N. Araj, Bruce Swihart, Robert Morrison, Patricia Gonzales Hurtado, Andrew Teo, Almahamoudou Mahamar, Oumar Attaher, Bacary S. Diarra, Santara Gaoussou, Djibrilla Issiaka, Alassane Dicko, Patrick E. Duffy, Michal Fried
Summary: The study utilized proteomic analyses of PfEMP1 from clinical parasite isolates collected from Malian children to identify targets of immunity. Peptide-specific antibody responses in children were examined, and it was found that high antibody levels to specific PfEMP1 domains correlated with decreased parasite burden in future infections. These findings suggest that certain PfEMP1 domains play a role in protective immunity against malaria.
Editorial Material
Immunology
Raphael A. Reyes, Rolando Garza, Evelien M. Bunnik
Summary: In this study, researchers isolated human monoclonal antibodies against two potential transmission-blocking vaccine candidates for malaria, Pfs48/45 and Pfs230, and identified the epitopes responsible for their transmission-reducing activity.
Article
Immunology
Hina Singh, Syed Yusuf Mian, Alok K. Pandey, Sri Krishna, Gaurav Anand, K. Sony Reddy, Neha Chaturvedi, Vanndita Bahl, Nidhi Hans, Man Mohan Shukla, Quique Bassat, Alfredo Mayor, Kazutoyo Miura, Praveen K. Bharti, Carole Long, Neeru Singh, Virander Singh Chauhan, Deepak Gaur
Summary: This study evaluated 25 triple antibody combinations for parasite neutralization activity against clinical isolates and identified the MSP-Fu+CyRPA+RH5 antibody combination as having the maximal neutralization effect against variable P. falciparum parasites. This suggests that these antibody combinations could be promising candidate antigens for a potential blood-stage malaria vaccine.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Immunology
Liriye Kurtovic, Tanmaya Atre, Gaoqian Feng, Bruce D. Wines, Jo-Anne Chan, Michelle J. Boyle, Damien R. Drew, P. Mark Hogarth, Freya J. Fowkes, Elke S. Bergmann-Leitner, James G. Beeson
Summary: The study found that RTS,S-induced antibodies in healthy adults can mediate Fc-dependent effector functions, with the highest functional antibodies generally observed after the second vaccine dose and targeting multiple regions of CSP. Participants with higher levels of functional antibodies had a reduced probability of developing parasitemia following homologous challenge.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Multidisciplinary Sciences
Raj Kumar Sah, Soumya Pati, Monika Saini, Shailja Singh
Summary: The sphingolipid pool plays a crucial role in regulating cellular functions in Plasmodium falciparum, and the parasite co-opts sphingolipids from host erythrocytes for its growth. By inhibiting SphK, the growth and development of P. falciparum can be inhibited, highlighting the importance of endogenous S1P in erythrocytes for parasite growth. Plasma S1P levels have no significant effect on Plasmodium growth, indicating a host-mediated effect.
SCIENTIFIC REPORTS
(2021)
Review
Immunology
Dilini Rathnayake, Elizabeth H. Aitken, Stephen J. Rogerson
Summary: This article discusses how antibody-mediated complement activation plays a role in protective immunity against malaria through different pathways. Antibodies form immune complexes with complement-fixing ability, effectively clearing parasites. The article also mentions the impact of complement receptor internalization on eliminating the harmful consequences of complement activation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Wai Kwan Tang, Camila H. Coelho, Kazutoyo Miura, Bergeline C. Nguemwo Tentokam, Nichole D. Salinas, David L. Narum, Sara A. Healy, Issaka Sagara, Carole A. Long, Patrick E. Duffy, Niraj H. Tolia
Summary: Pfs230D1 is a highly functional vaccine antigen for malaria transmission-blocking, and this study characterized a panel of human monoclonal antibodies (hmAbs) elicited in vaccinees immunized with Pfs230D1. The results showed diverse transmission-reducing activity of these hmAbs, but all bound to Pfs230D1 with nanomolar affinity. By constructing a high-resolution epitope map, the researchers identified that potent transmission-reducing hmAbs bound to one side of Pfs230D1, while non-potent hmAbs bound to the other side, and the second domain of Pfs230D1 occluded the epitopes for non-potent hmAbs. This study provides valuable insights for the structure-based design of enhanced immunogens and the development of diagnostic assays for measuring the transmission-reducing response.
Article
Immunology
Adela Nacer, Gaily Kivi, Raini Pert, Erkki Juronen, Pavlo Holenya, Eduardo Aliprandini, Rogerio Amino, Olivier Silvie, Doris Quinkert, Yann Le Duff, Matthew Hurley, Ulf Reimer, Andres Tover, Simon J. Draper, Sarah Gilbert, Mei Mei Ho, Paul W. Bowyer
Summary: Malaria, caused by Plasmodium parasites, is a global health issue with a significant number of cases and deaths each year. Resistance to current treatments emphasizes the need for the development of vaccines. This study focuses on the development of recombinant human antibodies to key target proteins and obtains potent antibodies that can be used for research and clinical trials.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Thayne H. H. Dickey, Richi Gupta, Holly McAleese, Tarik Ouahes, Sachy Orr-Gonzalez, Rui Ma, Olga Muratova, Nichole D. D. Salinas, Jen C. C. Hume, Lynn E. E. Lambert, Patrick E. E. Duffy, Niraj H. H. Tolia
Summary: A malaria vaccine that blocks parasite transmission from human to mosquito is being developed using the antigen Pfs48/45. The third domain of Pfs48/45 (D3) has potential as a transmission blocking vaccine (TBV), but production challenges have hindered its development. A computational design and screening process has been used to create a stabilized non-glycosylated form of the Pfs48/45 D3 antigen with improved characteristics, which can be genetically fused to a nanoparticle for vaccine production. This enhanced antigen enables new approaches to TBV development and can be applied to the design of other vaccine antigens.
Article
Microbiology
Isabell Berneburg, Satyamaheshwar Peddibhotla, Kim C. Heimsch, Kristina Haeussler, Patrick Maloney, Palak Gosalia, Janina Preuss, Mahsa Rahbari, Oleksii Skorokhod, Elena Valente, Daniela Ulliers, Luigi Felice Simula, Kathrin Buchholz, Michael P. Hedrick, Paul Hershberger, Thomas D. Y. Chung, Michael R. Jackson, Evelin Schwarzer, Stefan Rahlfs, Lars Bode, Katja Becker, Anthony B. Pinkerton
Summary: This study reports on a highly selective PfGluPho inhibitor, SBI-0797750, which shows potent activity against Plasmodium parasites. The compound disturbs the redox potential and H2O2 homeostasis of the parasites, without harming red blood cell integrity and phagocytosis.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Medicine, Research & Experimental
Emmanuel Amlabu, Prince B. Nyarko, Grace Opoku, Damata Ibrahim-Dey, Philip Ilani, Henrietta Mensah-Brown, Grace A. Akporh, Ojo-Ajogu Akuh, Evelyn A. Ayugane, David Amoh-Boateng, Kwadwo A. Kusi, Gordon A. Awandare
Summary: This study characterized a novel protein (PF3D7_1459400) and identified its potential role in erythrocyte invasion by Plasmodium falciparum, suggesting it as a potential target for blood-stage malaria vaccine development. The research also found naturally acquired plasma antibodies against PF3D7_1459400 protein in adults residing in malaria endemic regions in Ghana, indicating its immunogenicity. Overall, these findings highlight the importance of PF3D7_1459400 protein in the development of peptide-based vaccines for malaria.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Rakhee Lohia, Benoit Allegrini, Laurence Berry, Helene Guizouarn, Rachel Cerdan, Manouk Abkarian, Dominique Douguet, Eric Honore, Kai Wengelnik
Summary: A gain-of-function variant (E756del) in the PIEZO1 channel prevents severe malaria. Activation of PIEZO1 by Yoda1 and Jedi2 inhibitors induces echinocytosis and dehydration of red blood cells, inhibiting invasion by Plasmodium falciparum.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Immunology
Margaux Chauvet, Cerina Chhuon, Joanna Lipecka, Sebastien Dechavanne, Celia Dechavanne, Murielle Lohezic, Margherita Ortalli, Damien Pineau, Jean-Antoine Ribeil, Sandra Manceau, Caroline Le Van Kim, Adrian J. F. Luty, Florence Migot-Nabias, Slim Azouzi, Ida Chiara Guerrera, Anais Merckx
Summary: This passage discusses the possible reasons for the high prevalence of sickle cell disease in certain populations may be related to the protective effect of HbS against severe malaria caused by Plasmodium falciparum. By studying protein phosphorylation, it reveals the impact of HbS heterozygous carriage on the phosphorylation of proteins in red blood cell membranes and skeletal proteins, as well as parasite proteins during infection with malaria, which may lead to a less severe manifestation of malaria symptoms.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Damien R. Drew, Danny W. Wilson, Gretchen E. Weiss, Lee M. Yeoh, Isabelle G. Henshall, Brendan S. Crabb, Sheetij Dutta, Paul R. Gilson, James G. Beeson
Summary: The binding of AMA1 to RON2 is not essential for invasion and additional AMA1 interactions are involved. Antibodies targeting AMA1 domain 3 had greater invasion-inhibitory activity when RON2-loop binding was ablated, suggesting this domain is a promising additional target for vaccine development.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biology
J. Stephan Wichers, Gerry Tonkin-Hill, Thorsten Thye, Ralf Krumkamp, Benno Kreuels, Jan Strauss, Heidrun von Thien, Judith A. M. Scholz, Helle Smedegaard Hansson, Rasmus Weisel Jensen, Louise Turner, Freia-Raphaella Lorenz, Anna Schollhorn, Iris Bruchhaus, Egbert Tannich, Rolf Fendel, Thomas D. Otto, Thomas Lavstsen, Tim W. Gilberger, Michael F. Duffy, Anna Bachmann
Summary: The study found that parasite with PfEMP1 variants that bind to the endothelial protein C receptor (EPCR) were associated with severe malaria, while those binding to CD36 were linked to non-severe outcomes. First-time infected adults are more likely to develop severe symptoms, indicating that certain pathogenic PfEMP1 variants are more common in patients with naive immune systems.
Article
Biochemistry & Molecular Biology
Adam J. Blanch, Juan Nunez-Iglesias, Arman Namvar, Sebastien Menant, Oliver Looker, Vijay Rajagopal, Wai-Hong Tham, Leann Tilley, Matthew W. A. Dixon
Summary: The study demonstrates that as reticulocytes mature into RBCs, there is a decrease in cell surface area and an increase in the density of the spectrin-actin network, along with slight increases in inter-junctional distance and junctional density. Additionally, the edge region of mature RBCs contains more junctional complexes compared to the dimple region, supported by a 2% increase in band 4.1 density.
JOURNAL OF STRUCTURAL BIOLOGY-X
(2022)
Article
Medicine, General & Internal
Zoe Shih-Jung Liu, Jetsumon Sattabongkot, Michael White, Sadudee Chotirat, Chalermpon Kumpitak, Eizo Takashima, Matthias Harbers, Wai-Hong Tham, Julie Healer, Chetan E. Chitnis, Takafumi Tsuboi, Ivo Mueller, Rhea J. Longley
Summary: The study in western Thailand monitored antibody kinetics in 34 patients after P. vivax infections, showing an increase in antibody levels within 1 week post infection followed by an exponential decay. IgG1 dominance and IgG3 sub-dominance were observed, with some proteins inducing long-lived IgM responses.
Article
Infectious Diseases
Caitlin Bourke, Eizo Takashima, Li-Jin Chan, Melanie H. Dietrich, Ramin Mazhari, Michael White, Jetsumon Sattabongkot, Wai-Hong Tham, Takafumi Tsuboi, Ivo Mueller, Rhea Longley
Summary: The study investigates the use of antibody responses to predict recent infection of Plasmodium vivax. The results suggest that antibody responses to different sized fragments of PvRBP2b protein can be used as predictors of recent P. vivax infection.
Article
Biochemistry & Molecular Biology
Hayley E. Bullen, Paul R. Sanders, Madeline G. Dans, Thorey K. Jonsdottir, David T. Riglar, Oliver Looker, Catherine S. Palmer, Betty Kouskousis, Sarah C. Charnaud, Tony Triglia, Mikha Gabriela, Molly Parkyn Schneider, Jo-Anne Chan, Tania F. de Koning-Ward, Jake Baum, James W. Kazura, James G. Beeson, Alan F. Cowman, Paul R. Gilson, Brendan S. Crabb
Summary: Infection with Plasmodium falciparum parasites leads to a significant number of deaths each year. Understanding the proteins involved in parasite invasion and growth within human erythrocytes is important for developing new therapeutic strategies. One of these proteins, P113, has been found to play a role in both invasion and intracellular processes. Through our investigation, we discovered that P113 interacts with the protein export machinery and various proteins associated with the parasite vacuole. Furthermore, disrupting P113 affects the architecture of the vacuole membrane. This research provides insights into the function of P113 and its potential as a target for malaria treatment.
MOLECULAR MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Stephanie Studniberg, Lisa J. Ioannidis, Retno A. S. Utami, Leily Trianty, Yang Liao, Waruni Abeysekera, Connie S. N. Li-Wai-Suen, Halina M. Pietrzak, Julie Healer, Agatha M. Puspitasari, Dwi Apriyanti, Farah Coutrier, Jeanne R. Poespoprodjo, Enny Kenangalem, Benediktus Andries, Pak Prayoga, Novita Sariyanti, Gordon K. Smyth, Alan F. Cowman, Ric N. Price, Rintis Noviyanti, Wei Shi, Alexandra L. Garnham, Diana S. Hansen
Summary: This study investigates the differences between individuals experiencing symptomatic and asymptomatic P. falciparum infection using a systems approach. The results show that asymptomatic malaria, despite having protective responses, still exhibits an immunosuppressive transcriptional signature, which may impact the control of parasites and the response to malaria vaccines.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anthony N. Hodder, Janni Christensen, Stephen Scally, Tony Triglia, Anna Ngo, Richard W. Birkinshaw, Brodie Bailey, Paola Favuzza, Melanie H. Dietrich, Wai-Hong Tham, Peter E. Czabotar, Kym Lowes, Zhuyan Guo, Nicholas Murgolo, Manuel de Lera Ruiz, John A. McCauley, Brad E. Sleebs, David Olsen, Alan F. Cowman
Summary: Plasmepsins IX and X are essential proteases in Plasmodium spp., and their inhibition by WM4 and WM382 has been studied. The research identified protein substrates and revealed differences in substrate binding for PMIX and PMX. The structural analysis of PMX provided insights into drug binding important for drug development.
Article
Biology
Michal Pasternak, Julie M. J. Verhoef, Wilson Wong, Tony Triglia, Michael J. Mlodzianoski, Niall Geoghegan, Cindy Evelyn, Ahmad Z. Wardak, Kelly Rogers, Alan F. Cowmarc
Summary: The RhopH complex is not formed during merozoite invasion. Clag3 is released directly into the host cell cytoplasm, while RhopH2 and RhopH3 are released into the nascent parasitophorous vacuole. Export of RhopH2 and RhopH3 from the parasitophorous vacuole into the infected erythrocyte cytoplasm enables assembly of the Clag3/RhopH2/RhopH3 complex and its incorporation into the host cell membrane concomitant with activation of nutrient uptake.
COMMUNICATIONS BIOLOGY
(2022)
Article
Chemistry, Medicinal
Lachlan W. Richardson, Trent D. Ashton, Madeline G. Dans, Nghi Nguyen, Paola Favuzza, Tony Triglia, Anthony N. Hodder, Anna Ngo, Kate E. Jarman, Alan F. Cowman, Brad E. Sleebs
Summary: Plasmepsin X is an important aspartyl protease in the invasion and egression of Plasmodium parasites. In this study, peptidomimetics were designed to inhibit Plasmepsin X and effectively arrested the development of asexual Plasmodium falciparum parasites. These findings are significant for understanding the substrate specificity of Plasmepsin X and designing future antimalarial drugs.
Correction
Immunology
Bruce D. Wines, Liriye Kurtovic, Halina M. Trist, Sandra Esparon, Ester Lopez, Klasina Chappin, Li-Jin Chan, Francesca L. Mordant, Wen Shi Lee, Nicholas A. Gherardin, Sheila K. Patel, Gemma E. Hartley, Phillip Pymm, James P. Cooney, James G. Beeson, Dale I. Godfrey, Louise M. Burrell, Menno C. van Zelm, Adam K. Wheatley, Amy W. W. Chung, Wai-Hong Tham, Kanta Subbarao, Stephen J. Kent, P. Mark Hogarth
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Brook Jeang, Ming-Chieh Lee, Paula Embury, Delenasaw Yewhalaw, David Narum, Christopher King, Wai-Hong Tham, James Kazura, Guiyun Yan, Arlene Dent
Summary: This study aimed to evaluate a panel of 10 serological markers as a proxy for malaria exposure and determine the risk factors of seropositivity. The findings showed that seroprevalence and antibody levels to specific Plasmodium antigens can be used to identify high-risk groups and geographical areas where targeted interventions should be implemented.
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2023)
Article
Multidisciplinary Sciences
Tony Triglia, Stephen W. Scally, Benjamin A. Seager, Michal Pasternak, Laura F. Dagley, Alan F. Cowman
Summary: The authors characterized the function of the aspartic protease PMX and its role in activating the PCRCR complex, which is involved in erythrocyte invasion by Plasmodium falciparum. This study provides important insights into the essential role of PMX and the fine regulation of PCRCR function in P. falciparum biology.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Martin A. . Lowe, Alvaro Cardenas, Jean-Pierre Valentin, Zhaoning Zhu, Jan Abendroth, Jose L. Castro, Reiner Class, Annie Delaunois, Renaud Fleurance, Helga Gerets, Vitalina Gryshkova, Lloyd King, Donald D. Lorimer, Malcolm MacCoss, Julian H. Rowley, Marie-Luce Rosseels, Leandro Royer, Richard D. Taylor, Melanie Wong, Oliver Zaccheo, Vishal P. Chavan, Gokul A. . Ghule, Bapusaheb K. Tapkir, Jeremy N. Burrows, Maelle Duffey, Matthias Rottmann, Sergio Wittlin, Inigo Angulo-Barturen, Maria Belen Jimenez-Diaz, Josefine Striepen, Kate J. Fairhurst, Tomas Yeo, David A. . Fidock, Alan F. Cowman, Paola Favuzza, Benigno Crespo-Fernandez, Francisco Javier Gamo, Daniel E. Goldberg, Dominique Soldati-Favre, Benoit Laleu, Teresa de Haro
Summary: This study optimized Plasmepsin X (PMX) and identified potent PMX inhibitors with potential efficacy in treating malaria.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Immunology
Samantha K. Davis, Kevin John Selva, Ester Lopez, Ebene R. Haycroft, Wen Shi Lee, Adam K. Wheatley, Jennifer A. Juno, Amy Adair, Phillip Pymm, Samuel J. Redmond, Nicholas A. Gherardin, Dale Godfrey, Wai-Hong Tham, Stephen J. Kent, Amy W. Chung
Summary: Convalescent plasma IgA contributed to the neutralising antibody response of wild-type SARS-CoV-2 RBD and various RBD mutations, but its potency was less than IgG. Plasma IgA from early convalescent COVID-19 subjects showed the capacity to inhibit the interaction between wild-type RBD and ACE2, and in some cases, exhibited stronger ACE2 inhibition than matched IgG. However, plasma IgA was largely incapable of mediating antibody-dependent phagocytosis compared to plasma IgG.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2022)
Article
Cell Biology
Rhea J. Longley, Matthew J. Grigg, Kael Schoffer, Thomas Obadia, Stephanie Hyslop, Kim A. Piera, Narimane Nekkab, Ramin Mazhari, Eizo Takashima, Takafumi Tsuboi, Matthias Harbers, Kevin Tetteh, Chris Drakeley, Chetan E. Chitnis, Julie Healer, Wai-Hong Tham, Jetsumon Sattabongkot, Michael T. White, Daniel J. Cooper, Giri S. Rajahram, Bridget E. Barber, Timothy William, Nicholas M. Anstey, Ivo Mueller
Summary: Serological markers are a promising tool for surveillance and interventions for malaria. This study found that IgG antibody reactivity is high against P. vivax proteins with high sequence identity with their P. knowlesi ortholog. A panel of eight P. vivax proteins with low levels of cross-reactivity with P. knowlesi has been designed, which can accurately classify recent P. vivax infections and reduce misclassification of recent P. knowlesi infections.
CELL REPORTS MEDICINE
(2022)