Article
Immunology
Susheel K. Singh, Jordan Plieskatt, Bishwanath K. Chourasia, Amanda Fabra-Garcia, Asier Garcia-Senosiain, Vandana Singh, Karin Lovgren Bengtsson, Jenny M. Reimer, Robert Sauerwein, Matthijs M. Jore, Michael Theisen
Summary: This study presents a scalable and reproducible process for manufacturing R0.6C under cGMP, resulting in a sufficient yield for clinical evaluation. Various analytical assays were established to assess the identity, release, and stability of R0.6C, confirming its potential for use as a malaria transmission-blocking vaccine. Preclinical studies demonstrated that R0.6C elicited functional antibodies and showed enhanced response when combined with adjuvant.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Roos M. de Jong, Susheel K. Singh, Karina Teelen, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Will J. R. Stone, Emily Locke, Jordan Plieskatt, Michael Theisen, Teun Bousema, Matthijs M. Jore
Summary: Researchers analyzed sera from naturally exposed individuals and found that the presence and/or intensity of antibodies against 12 novel putative surface expressed gametocyte antigens was associated with transmission reducing activity. Protein fragments of these antigens were successfully designed and expressed in different cells. All tested antigens were recognized by antibodies from individuals living in malaria-endemic areas and induced antigen-specific antibody responses in mice. However, none of these antigens induced an antibody response that reduced parasite development in the mosquito midgut.
FRONTIERS IN IMMUNOLOGY
(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
Immunology
Susheel K. Singh, Jordan Plieskatt, Bishwanath K. Chourasia, Vandana Singh, Karin Lovgren Bengtsson, Jenny M. Reimer, Renate C. van Daalen, Karina Teelen, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Matthijs M. Jore, Michael Theisen
Summary: The modified construct ProC6C successfully improved expression levels, paving the way for further clinical evaluation. A scalable process in the Lactococcus lactis expression system was developed, along with a panel of analytical assays for release and stability. Immunogenicity studies in mice demonstrated that ProC6C can induce functional antibodies that reduce transmission to mosquitoes and invasion of human hepatocytes.
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
Chemistry, Medicinal
Giulia Siciliano, Veronica Di Paolo, Dante Rotili, Rossella Migale, Francesca Pedini, Marialuisa Casella, Serena Camerini, Daniele Dalzoppo, Rob Henderson, Tonnie Huijs, Koen J. Dechering, Antonello Mai, Anna Maria Caccuri, Marco Lalle, Luigi Quintieri, Pietro Alano
Summary: This work investigates the activity of NBDHEX and its carboxylic acid metabolite on the human malaria parasite Plasmodium falciparum. NBDHEX shows strong activity against all blood stages of the parasite, with a higher potency against the gametocytes. Covalent modifications of gametocyte proteins are found to be associated with the antiparasitic effect of NBDHEX. Both NBDHEX and its metabolite have limited cytotoxicity in vitro, making them potential starting points for the development of new drugs to block malaria transmission.
Article
Multidisciplinary Sciences
Joseph D. Challenger, Daniela Olivera Mesa, Dari F. Da, R. Serge Yerbanga, Thierry Lefevre, Anna Cohuet, Thomas S. Churcher
Summary: Transmission-blocking vaccines for malaria are being tested and their field efficacy is predicted to be higher than in laboratory conditions. Targeting school-aged children is recommended as it can have a significant impact in reducing malaria cases. Utilizing such vaccines alongside existing interventions could have substantial benefits in malaria control.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Rebecca Webster, Hayley Mitchell, Jenny M. Peters, Juanita Heunis, Brighid O'Neill, Jeremy Gower, Sean Lynch, Helen Jennings, Fiona H. Amante, Stacey Llewellyn, Louise Marquart, Adam J. Potter, Geoffrey W. Birrell, Michael D. Edstein, G. Dennis Shanks, James S. McCarthy, Bridget E. Barber
Summary: A single low dose of tafenoquine can effectively reduce the transmission of Plasmodium falciparum parasites to mosquitoes, although there is a delay in its effect.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Medicine, General & Internal
Melissa D. Conrad, Victor Asua, Shreeya Garg, David Giesbrecht, Karamoko Niare, Sawyer Smith, Jane F. Namuganga, Thomas Katairo, Jennifer Legac, Rebecca M. Crudale, Patrick K. Tumwebaze, Samuel L. Nsobya, Roland A. Cooper, Moses R. Kamya, Grant Dorsey, Jeffrey A. Bailey, Philip J. Rosenthal
Summary: This study identified multifocal emergence and spread of Plasmodium falciparum with partial resistance to artemisinins in Uganda. The emergence and spread of resistance were predominantly observed in areas where effective malaria control had been discontinued or transmission was unstable.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Parasitology
Pornpawee Sookpongthai, Korawich Utayopas, Thassanai Sitthiyotha, Theerakamol Pengsakul, Morakot Kaewthamasorn, Kittikhun Wangkanont, Pongchai Harnyuttanakorn, Surasak Chunsrivirot, Sittiporn Pattaradilokrat
Summary: This study investigated the global diversity of Pfs25 in P. falciparum populations, identifying 11 unique haplotypes, with H1 and H2 as the major haplotypes. The distribution patterns of these haplotypes varied across different geographical populations, with limited polymorphism likely due to negative selection.
PARASITES & VECTORS
(2021)
Article
Immunology
Amanda Fabra-Garcia, Sophia Hailemariam, Roos M. de Jong, Kirsten Janssen, Karina Teelen, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Danton Ivanochko, Anthony Semesi, Brandon McLeod, Martijn W. Vos, Marloes H. C. de Bruijni, Judith M. Bolscher, Marta Szabat, Stefanie Vogt, Lucas Kraft, Sherie Duncan, Moses R. Kamya, Margaret E. Feeney, Prasanna Jagannathan, Bryan Greenhouse, Koen J. Dechering, Robert W. Sauerwein, C. Richter King, Randall S. MacGill, Teun Bousema, Jean-Philippe Julien, Matthijs M. Jore
Summary: Malaria transmission-blocking vaccines aim to induce antibodies that interrupt parasite development in mosquitoes, providing a tool for malaria control. We isolated and characterized 81 human monoclonal antibodies specific to the Pfs48/45 protein, a leading vaccine candidate. Potent antibodies targeting specific domains achieved high transmission-reducing activity. Co-crystal structures identified protective epitopes, providing insight for refined vaccine design.
Article
Multidisciplinary Sciences
Brendan Fries, Carlos A. Guerra, Guillermo A. Garcia, Sean L. Wu, Jordan M. Smith, Jeremias Nzamio Mba Oyono, Olivier T. Donfack, Jose Osa Osa Nfumu, Simon Hay, David L. Smith, Andrew J. Dolgert
Summary: Different population layers performed differently in matching the gold standard distribution at different population densities. Choosing the appropriate population map has a significant impact on burden estimates in a malaria model.
Article
Food Science & Technology
Xin Shen, Weicheng Li, Hongyu Cai, Shuai Guo, Min Li, Yangshuo Liu, Zhihong Sun
Summary: This study analyzed the fermentation capacity and metabolic profiles of 17 L. lactis subsp. lactis strains and found significant metabolic differences between strains with different fermentation rates. Peptides, esters, and tributyrin were identified as biomarkers to distinguish between fast and slow fermentation groups.
FOOD RESEARCH INTERNATIONAL
(2022)
Article
Multidisciplinary Sciences
Kuang-Ting Ko, Frank Lennartz, David Mekhaiel, Bora Guloglu, Arianna Marini, Danielle J. Deuker, Carole A. Long, Matthijs M. Jore, Kazutoyo Miura, Sumi Biswas, Matthew K. Higgins
Summary: Researchers have determined the structure of the Pfs48/45 protein, a potential candidate for a malaria vaccine, and identified antibodies that can block transmission of the parasite. These findings will help in developing future Pfs48/45-based vaccines.
NATURE COMMUNICATIONS
(2022)
Article
Agriculture, Multidisciplinary
Bibek Byanju, Swastik Sen, Thomas Mansell, Buddhi P. P. Lamsal
Summary: Corn steep liquor (CSL) and thin stillage were evaluated as growth media for recombinant Lactococcus lactis to produce antifreeze proteins (AFPs). Light CSL and thin stillage were optimized with additives and trace elements to enhance the growth of wild-type and recombinant strains. The fermentation supernatants showed longer times to supercool and freeze, indicating potential use as antifreeze compounds in frozen food and non-food applications.
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
(2023)
Article
Immunology
Roos M. de Jong, Susheel K. Singh, Karina Teelen, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Will J. R. Stone, Emily Locke, Jordan Plieskatt, Michael Theisen, Teun Bousema, Matthijs M. Jore
Summary: Researchers analyzed sera from naturally exposed individuals and found that the presence and/or intensity of antibodies against 12 novel putative surface expressed gametocyte antigens was associated with transmission reducing activity. Protein fragments of these antigens were successfully designed and expressed in different cells. All tested antigens were recognized by antibodies from individuals living in malaria-endemic areas and induced antigen-specific antibody responses in mice. However, none of these antigens induced an antibody response that reduced parasite development in the mosquito midgut.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Selorme Adukpo, Ayodele Adedoja, Meral Esen, Michael Theisen, Francine Ntoumi, Olusola Ojurongbe
Summary: This study found that hookworm and H. nana infections are associated with reduced GMZ2 specific IgG levels, indicating potential manipulation of immune responses by helminths for their survival and transmission, which may have serious implications for vaccine development and deployment in helminth-endemic regions.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Joey Sheff, John Kelly, Mary Foss, Eric Brunette, Kristin Kemmerich, Henk van Faassen, Shalini Raphael, Greg Hussack, Gerard Comamala, Kasper Rand, Danica B. Stanimirovic
Summary: This study investigates VHH-IR4, a single-domain antibody capable of crossing the blood-brain barrier (BBB) and binding to IGF1R. The binding site of VHH-IR4 was identified within the cysteine-rich region (CRR) of IGF1R, and its inhibition of ligand-induced auto-phosphorylation was examined. These findings provide valuable insights for the development of antibodies with improved BBB trafficking and optimized IGF1R binding characteristics.
JOURNAL OF BIOCHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Abdou Khadre Dit Jadir Fall, Ikhlaq Hussain Kana, Asier Garcia-Senosiain, Benoit Henry, Celia Dechavanne, Andre Garcia, Pierre Buffet, Audrey Sabbagh, Florence Migot-Nabias, Michael Theisen, David Courtin
Summary: This study explores a potential mechanism of natural protection against malaria in the Fulani population, suggesting that antibody-mediated merozoite phagocytosis may play a role. Results show that adults from the Bariba, Otamari, and Gando groups have higher levels of opsonic phagocytosis compared to children, while the Fulani population shows the opposite trend. Fulani children have higher levels of opsonic phagocytosis and anti-GLURP antibodies compared to non-Fulani children, with no significant difference observed in Fulani adults. Higher levels of opsonic phagocytosis before the malaria transmission season are associated with negative malaria Rapid Diagnostic Test results after the season.
Article
Immunology
Eric Kyei-Baafour, Kwadwo Asamoah Kusi, Fareed K. N. Arthur, Regis W. Tiendrebeogo, Eunice Owusu-Yeboa, Susheel K. Singh, Sarah Friedrich, Thomas A. Gerds, Daniel Dodoo, Michael Theisen, Bright Adu
Summary: Opsonic phagocytosis and antibody-mediated merozoite growth inhibition play protective roles against malaria in Ghanaian children, and they may act independently. Vaccines incorporating RON4 may benefit from both immune mechanisms.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Barbara de Oliveira Baptista, Ana Beatriz Lopes de Souza, Luana Santos de Oliveira, Hugo Amorim dos Santos de Souza, Jenifer Peixoto de Barros, Lucas Tavares de Queiroz, Rodrigo Medeiros de Souza, Linda Eva Amoah, Susheel Kumar Singh, Michael Theisen, Rodrigo Nunes Rodrigues-da-Silva, Evelyn Kety Pratt Riccio, Paulo Renato Rivas Totino, Josue da Costa Lima Junior, Claudio Tadeu Daniel-Ribeiro, Lilian Rose Pratt-Riccio
Summary: The GMZ2.6c malaria vaccine candidate is a multi-stage protein that shows immunogenicity and immunodominance in individuals exposed to malaria. It contains fragments of Pfs48/45-6C protein fused to GMZ2, which consists of the N-terminal region of GLURP and the C-terminal region of MSP-3. The identified epitopes of GMZ2.6c, P11 and DG210, induced significant antibody responses and may play a role in the acquisition of protective immunity.
Article
Chemistry, Multidisciplinary
Christian Code, Danwen Qiu, Ilia A. Solov'yov, Jung-Goo Lee, Hyeon-Cheol Shin, Christopher Roland, Celeste Sagui, Damian Houde, Kasper D. Rand, Thomas J. D. Jorgensen
Summary: The fragmentation of protonated glycopeptides by collision-induced dissociation (CID) can be used to determine the solution-specific deuterium content of the glycan. However, the level of hydrogen/deuterium (H/D) scrambling depends on the backbone conformation and glycosylation pattern of the glycopeptides. Complete scrambling occurs before glycosidic bond cleavage in normal glycopeptides, while glycosidic bond cleavage occurs without scrambling in glycopeptide antibiotic vancomycin. Scrambling is also inhibited, to a lesser degree, in the conformationally restricted glycopeptides ristocetin and its pseudoaglycone.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemical Research Methods
Thomas Lambert, Marius Gramlich, Luisa Stutzke, Luke Smith, Dingyu Deng, Philipp D. Kaiser, Ulrich Rothbauer, Justin L. P. Benesch, Cornelia Wagner, Maximiliane Koenig, Petr Pompach, Petr Novak, Anne Zeck, Kasper D. Rand
Summary: Protein glycosylation is a common protein modification, but determining the HDX of glycosylated protein segments has been challenging. In this study, we developed a column containing PNGase Rc that can be integrated into a conventional HDX-MS setup to improve glycoprotein analysis. The PNGase Rc column enables efficient online removal of N-linked glycans and determination of glycosylated regions' HDX in complex glycoproteins. We also demonstrated the column's use in mapping the binding epitope of a mAb to c-Met, a complex glycoprotein drug target. Overall, our work shows that HDX-MS with the integrated PNGase Rc column allows fast and efficient deglycosylation under harsh quench conditions and provides comprehensive analysis of complex glycoproteins.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Multidisciplinary Sciences
Isabel Byrne, Timothy William, Tock H. Chua, Catriona Patterson, Tom Hall, Mark Tan, Chetan Chitnis, John Adams, Susheel K. Singh, Lynn Grignard, Kevin K. A. Tetteh, Kimberly M. Fornace, Chris J. Drakeley
Summary: Malaysia has not reported any indigenous cases of P. falciparum and P. vivax for over 3 years. A recent study in Malaysian Borneo used serology, risk-factor assessment, and geostatistical models to understand the exposure risks and demographic factors associated with malaria transmission. The study found low recent exposure to P. falciparum and identified forest activity and longer travel times to healthcare as common risk-factors for exposure to both P. falciparum and P. vivax.
SCIENTIFIC REPORTS
(2023)
Article
Biology
Ebenezer Addo Ofori, Asier Garcia-Senosiain, Mohammad Naghizadeh, Ikhlaq Hussain Kana, Morten Hanefeld Dziegiel, Bright Adu, Subhash Singh, Michael Theisen
Summary: Blood phagocytes generate reactive oxygen species (ROS) in response to infections. The study investigates how Fc gamma receptors induce ROS production in neutrophils, contributing to anti-malarial immunity. Both Fc gamma RIIIB and Fc gamma RIIA synergistically induce ROS production in neutrophils, involving NADPH oxidase 2 and the PI3K pathway. The high levels of neutrophil ROS are associated with protection against febrile malaria, highlighting the importance of the cooperation between anti-malarial IgG and neutrophils.
COMMUNICATIONS BIOLOGY
(2023)