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
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.
Review
Immunology
Eizo Takashima, Mayumi Tachibana, Masayuki Morita, Hikaru Nagaoka, Bernard N. Kanoi, Takafumi Tsuboi
Summary: Efforts to control malaria have seen success in the past two decades, but have been complicated by the emergence of COVID-19. Developing more effective malaria vaccines, especially transmission-blocking vaccines, is vital for the goal of malaria elimination. Challenges in TBV development highlight the need for novel approaches and accelerated candidate discovery.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
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)
Review
Chemistry, Medicinal
Sara Consalvi, Chiara Tammaro, Federico Appetecchia, Mariangela Biava, Giovanna Poce
Summary: Even though more research and a deeper understanding of parasite sexual stages biology are needed, the development of novel strategies to block transmission has significantly accelerated. Among the innovative patented inventions, the surface-delivery of antimalarial drugs to kill transmission-stages parasites in mosquitoes shows the highest promise for success in malaria control strategies, opening up new possibilities in malaria transmission-blocking drug discovery.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2022)
Article
Microbiology
Yaozheng Xu, Dan Qiao, Yuhao Wen, Yifei Bi, Yuxi Chen, Zhenghui Huang, Liwang Cui, Jian Guo, Yaming Cao
Summary: PfAP2-G2 plays a crucial role in regulating gametocyte development in Plasmodium falciparum, with its knockout resulting in a significant decrease in mature gametocytes and an impact on the gender ratio of gametocytes.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Microbiology
Achaporn Yipsirimetee, Pornpawee Chiewpoo, Rupam Tripura, Dysoley Lek, Nicholas P. J. Day, Arjen M. Dondorp, Sasithon Pukrittayakamee, Nicholas J. White, Kesinee Chotivanich
Summary: In this study, the activities of cipargamin, ganaplacide, and artesunate against artemisinin-resistant Plasmodium falciparum isolates were compared. Ganaplacide exhibited higher activities than cipargamin and artesunate, and both cipargamin and ganaplacide showed significant transmission-blocking activities against artemisinin-resistant Plasmodium falciparum.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
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
John Rek, Sara Lynn Blanken, Joseph Okoth, Daniel Ayo, Ismail Onyige, Eric Musasizi, Jordache Ramjith, Chiara Andolina, Kjerstin Lanke, Emmanuel Arinaitwe, Peter Olwoch, Katharine A. Collins, Moses R. Kamya, Grant Dorsey, Chris Drakeley, Sarah G. Staedke, Teun Bousema, Melissa D. Conrad
Summary: This study in a high malaria transmission area in Uganda found that school-aged children and asymptomatic infections are major contributors to the malaria human infectious reservoir. Understanding the transmissibility of human infections in different settings is crucial for achieving malaria elimination. It was determined that asymptomatic infections had a higher impact on transmission compared to symptomatic infections.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Review
Immunology
Gisele Tatiane Soares da Veiga, Matheus Ribeiro Moriggi, Jean Franciesco Vettorazzi, Marcelo Mueller-Santos, Letusa Albrecht
Summary: Malaria is a devastating infectious disease caused by Plasmodium parasites, and finding an effective vaccine is a major challenge. Plasmodium vivax, the second most prevalent species, has been neglected for decades, leading to a lack of knowledge and vaccine development. The main difficulties in developing a P. vivax vaccine are its high genetic diversity and complex life cycle. This review presents the main findings of vivax malaria vaccines to date to support future investigations.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Myriam Arevalo-Herrera, Kazutoyo Miura, Nora Cespedes, Carlos Echeverry, Eduardo Solano, Angelica Castellanos, Juan Sebastian Ramirez, Adolfo Miranda, Andrey V. Kajava, Carole Long, Giampietro Corradin, Socrates Herrera
Summary: The P48/45 antigen, a crucial factor in Plasmodium parasite fertilization, was found to be more immunoreactive when expressed in Chinese Hamster Ovary (CHO) cells compared to Escherichia coli, showing potential for use in a protein vaccine. While there was an age-dependent increase in response to both antigens, specific IgG antibodies to CHO-rPvs48/45 demonstrated functional activity in inhibiting parasite transmission, suggesting promising prospects for further research.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Melanie C. Ridgway, Daniela Cihalova, Simon H. J. Brown, Phuong Tran, Todd W. Mitchell, Alexander G. Maier
Summary: Male and female Plasmodium falciparum gametocytes play a key role in the transmission of malaria from human hosts to mosquito vectors. Research shows significant differences in lipid composition between male and female gametocytes, with female gametocytes enriched in cholesteryl esters and dihydrosphingomyelin. The study highlights the potential of targeting sex-specific gametocyte lipid metabolism as a strategy to block malaria transmission.
JOURNAL OF CELL SCIENCE
(2022)
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
Immunology
Michelle K. Muthui, Eizo Takashima, Brian R. Omondi, Christine Kinya, William I. Muasya, Hikaru Nagaoka, Kennedy W. Mwai, Benedict Orindi, Juliana Wambua, Teun Bousema, Chris Drakeley, Andrew M. Blagborough, Kevin Marsh, Philip Bejon, Melissa C. Kapulu
Summary: Naturally acquired immunity to gametocyte antigens plays a crucial role in interrupting transmission, influenced by age and concurrent parasitaemia. Novel candidates for evaluating transmission-blocking activity have been identified in this study.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Matthew B. Laurens
Summary: Malaria vaccines, including the RTS,S/AS01 vaccine, are showing moderate efficacy and new approaches are being developed for next-generation vaccines. Techniques such as RNA vaccine delivery and whole organism vaccination are being explored, with the goal of creating highly effective malaria vaccines that provide sustained protection.
HUMAN VACCINES & IMMUNOTHERAPEUTICS
(2021)
Article
Infectious Diseases
Barbara Oliveira Baptista, Ana Beatriz Lopes de Souza, Evelyn Kety Pratt Riccio, Cesare Bianco-Junior, Paulo Renato Rivas Totino, Joao Herminio Martins da Silva, Michael Theisen, Susheel Kumar Singh, Linda Eva Amoah, Marcelo Ribeiro-Alves, Rodrigo Medeiros Souza, Josue Costa Lima-Junior, Claudio Tadeu Daniel-Ribeiro, Lilian Rose Pratt-Riccio
Summary: The GMZ2.6c malaria vaccine candidate was found to be widely recognized by naturally acquired antibodies from individuals living in malaria-endemic areas in Brazil. The presence of antibodies against GMZ2.6c suggests an additive effect of its components GLURP, MSP-3, and Pfs48/45. Moreover, individuals exposed to malaria infection predominantly had cytophilic anti-GMZ2.6c antibodies, which may contribute to parasite immunity.
Article
Multidisciplinary Sciences
Katharina Braunger, Jiyoon Ahn, Matthijs M. Jore, Steven Johnson, Terence T. L. Tang, Dennis V. Pedersen, Gregers R. Andersen, Susan M. Lea
Summary: The authors report the identification and characterisation of a species-specific properdin inhibitor CirpA derived from tick saliva, opening avenues for future therapeutic approaches.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Amanda Fabra-Garcia, Annie S. P. Yang, Marije C. Behet, Zen Yap, Youri van Waardenburg, Swarnendu Kaviraj, Kjerstin Lanke, Geert-Jan Van Gemert, Matthijs M. Jore, Teun Bousema, Robert W. Sauerwein
Summary: Sporozoite-based vaccine strategies are effective in preventing Plasmodium falciparum malaria. The circum-sporozoite protein (CSP) is currently the main target for vaccine development, but this study found that antibodies targeting non-CSP proteins can also inhibit parasite invasion and development.
Article
Immunology
Katherine O'Flaherty, Jo-Anne Chan, Julia C. Cutts, Sophie G. Zaloumis, Elizabeth A. Ashley, Aung Pyae Phyo, Damien R. Drew, Arjen M. Dondorp, Nicholas P. Day, Mehul Dhorda, Rick M. Fairhurst, Pharath Lim, Chanaki Amaratunga, Sasithon Pukrittayakamee, Tran Tinh Hien, Ye Htut, Mayfong Mayxay, M. Abul Faiz, Olugbenga A. Mokuolu, Marie A. Onyamboko, Caterina Fanello, Eizo Takashima, Takafumi Tsuboi, Michael Theisen, Francois Nosten, James G. Beeson, Julie A. Simpson, Nicholas J. White, Freya J. Fowkes
Summary: The study found that Pfs230 and Pfs48/45 antibodies are associated with patent gametocytemia and increasing gametocyte density across multiple malaria endemic settings, including regions with emerging artemisinin-resistant P. falciparum.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Immunology
Sylvester Dassah, Bright Adu, Regis W. Tiendrebeogo, Susheel K. Singh, Fareed K. N. Arthur, Sodiomon B. Sirima, Michael Theisen
Summary: In a study conducted in Banfora, Burkina Faso, the antibody responses and naturally acquired immunity associated with malaria incidence were evaluated for the malaria vaccine candidate GMZ2. The study found that the efficacy of GMZ2 vaccine varied by age group, with higher efficacy in children aged 36-60 months. The analysis also identified other antigens that may be associated with reduced incidence of malaria.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Public, Environmental & Occupational Health
Robert W. Sauerwein, Jordan Plieskatt, Michael Theisen
Summary: Pfs48/45 is a critical protein of the sexual stages of Plasmodium falciparum, and antibodies against it can prevent parasite development and the spread of malaria. However, manufacturing challenges delayed its clinical development for 20 years, and the first clinical trial just started recently.
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2022)
Article
Infectious Diseases
Odilon Nouatin, Javier Ibanez, Rolf Fendel, Ulysse A. Ngoa, Freia-Raphaella Lorenz, Jean-Claude Dejon-Agobe, Jean Ronald Edoa, Judith Fluegge, Sina Brueckner, Meral Esen, Michael Theisen, Stephen L. Hoffman, Kabirou Moutairou, Adrian J. F. Luty, Bertrand Lell, Peter G. Kremsner, Ayola A. Adegnika, Benjamin Mordmueller
Summary: In a vaccine trial investigating the malaria vaccine candidate GMZ2, it was found that the GMZ2-specific antibody response increased after vaccination but was not correlated to protection. However, antibody responses to several Plasmodium falciparum antigens and the broadness of malaria-specific antibody response were significantly higher in protected study participants.
Review
Parasitology
Maartje R. Inklaar, Carolina Barillas-Mury, Matthijs M. Jore
Summary: This article provides an in-depth overview of the evasion mechanisms currently known for the malaria parasite, Plasmodium. It also speculates on the existence of other unidentified mechanisms. These mechanisms could potentially serve as novel targets for urgently needed malaria vaccines and therapeutics.
TRENDS IN PARASITOLOGY
(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
Biochemistry & Molecular Biology
Abdou Khadre Dit Jadir Fall, David Courtin, Rafiou Adamou, Sofie Edslev, Anita Hansen, Nadia Domingo, Michael Christiansen, Bright Adu, Jacqueline Milet, Andre Garcia, Michael Theisen, Florence Migot-Nabias, Celia Dechavanne
Summary: This study investigated the influence of polymorphisms in the FCGR2A gene and the FCGR3B gene on malaria susceptibility and antibody responses in Beninese children. The results highlighted the impact of FCGR3B polymorphisms on individual susceptibility to malaria and antibody responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Infectious Diseases
Abdou Khadre Dit Jadir Fall, Ikhlaq Hussain Kana, Celia Dechavanne, Asier Garcia-Senosiain, Evelyne Guitard, Jacqueline Milet, Achille Massougbodji, Andre Garcia, Jean-Michel Dugoujon, Florence Migot-Nabias, Michael Theisen, David Courtin
Summary: This study highlights the importance of IgG antibodies to merozoite surface antigens in controlling asymptomatic malaria infection in Beninese infants. Additionally, the study demonstrates the impact of G3m phenotypes on the functional activity of IgG, which could be valuable in the development of vaccines against malaria parasites or other pathogens.
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
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)
