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)
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
Multidisciplinary Sciences
Li-Jin Chan, Anugraha Gandhirajan, Lenore L. Carias, Melanie H. Dietrich, Oscar Vadas, Remy Visentin, Camila T. Franca, Sebastien Menant, Dominique Soldati-Favre, Ivo Mueller, Christopher L. King, Wai-Hong Tham
Summary: The study shows that antibodies against Plasmodium vivax RBP2b can provide protection against infection and disease, and inhibit invasion of reticulocytes. Researchers have identified different mechanisms by which human antibodies can inhibit the invasion ability of P. vivax RBP2b.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Sophie Uyoga, Perpetual Wanjiku, Jesse C. Rop, Johnstone Makale, Alexander W. Macharia, Gideon M. Nyutu, Mohammed Shebe, Kennedy A. Awuondo, Neema Mturi, Charles J. Woodrow, Arjen M. Dondorp, Kathryn Maitland, Thomas N. Williams
Summary: The clinical severity of Plasmodium falciparum malaria infections is directly related to the total parasite load, with higher parasite counts found in uncomplicated cases. The concentration of PfHRP2 also increases with severity, except in cases of severe malaria with concomitant bacterial infections where it is significantly lower. A quantitative test for plasma concentrations of PfHRP2 may aid in identifying children at the greatest clinical risk and differentiating critically ill children with malaria as a secondary cause.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Immunology
Colleen M. Leonard, Ashenafi Assefa, Heven Sime, Hussein Mohammed, Amha Kebede, Hiwot Solomon, Chris Drakeley, Matt Murphy, Jimee Hwang, Eric Rogier
Summary: Assessing the spatial distribution of malaria exposure using multiple metrics can improve understanding of malaria transmission dynamics in a region. In low-transmission areas, antibody data provide a useful marker to assess malaria exposure. This study conducted blood sample assessments in three regions in Ethiopia, showing low prevalence of malaria infection.
JOURNAL OF INFECTIOUS DISEASES
(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
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
Multidisciplinary Sciences
Gaoqian Feng, Bruce D. Wines, Liriye Kurtovic, Jo-Anne Chan, Philippe Boeuf, Vanessa Mollard, Anton Cozijnsen, Damien R. Drew, Rob J. Center, Daniel L. Marshall, Sandra Chishimba, Geoffrey McFadden, Arlene E. Dent, Kiprotich Chelimo, Michelle J. Boyle, James W. Kazura, P. Mark Hogarth, James G. Beeson
Summary: Understanding mechanisms of antibody-mediated immunity is crucial for developing highly protective vaccines against malaria. Our study identified key roles of Fc gamma-receptor interactions and phagocytosis in humoral immunity, highlighting specific targets and mechanisms that could maximize vaccine efficacy. Antibodies play critical roles in adaptive immune responses to infectious agents, with Fc gamma-receptors being essential for their activity against Plasmodium falciparum sporozoites.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Jonathan B. Parr, Eddy Kieto, Fernandine Phanzu, Paul Mansiangi, Kashamuka Mwandagalirwa, Nono Mvuama, Ange Landela, Joseph Atibu, Solange Umesumbu Efundu, Jean W. Olenga, Kyaw Lay Thwai, Camille E. Morgan, Madeline Denton, Alison Poffley, Jonathan J. Juliano, Pomie Mungala, Joris L. Likwela, Eric M. Sompwe, Eric Rogier, Antoinette K. Tshefu, Adrien N'Siala, Albert Kalonji
Summary: The majority of malaria diagnoses in Africa are made using RDTs that detect histidine-rich protein 2, but concerns have been raised about false-negative results due to parasites with deletions in the pfhrp2/3 genes. A study in the Democratic Republic of the Congo found that HRP2-based RDTs remain appropriate for detecting malaria, despite the presence of parasites with deletions in pfhrp2/3.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Katharina Preissinger, Miklos Kellermayer, Beata G. Vertessy, Istvan Kezsmarki, Janos Torok
Summary: Malaria, a global burden with millions of annual cases, requires improvement in diagnostic techniques for its elimination. This study introduces a novel neural network-based scheme capable of high-speed and accurate classification of malaria infected red blood cells. The smart reduction of data dimension significantly improves the performance and applicability of the method.
SCIENTIFIC REPORTS
(2022)
Review
Multidisciplinary Sciences
Yonas Yimam, Mehdi Mohebali, Mohammad Javad Abbaszadeh Afshar
Summary: This study compared the diagnostic performance of a new ultrasensitive rapid diagnostic test (us-RDT) and a conventional rapid diagnostic test (co-RDT) for detecting malaria. The results showed that us-RDT had higher sensitivity, especially in asymptomatic individuals and low transmission areas.
Review
Pathology
Loick P. Kojom Foko, Jahnvi Jakhan, Geetika Narang, Vineeta Singh
Summary: This review provides an overview of field findings on sequence variation of Plasmodium falciparum histidine-rich proteins 2/3 (PfHRP2/3) and its critical impact on PfHRP2-based rapid diagnostic test (RDT) detection. The study found that PfHRP2/3 are highly polymorphic, but current findings are insufficient to conclude on their role in RDT detection.
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
(2023)
Article
Immunology
Niharika Shukla, Wai Kwan Tang, Camila H. Coelho, Carole A. Long, Sara A. Healy, Issaka Sagara, Kazutoyo Miura, Patrick E. Duffy, Niraj H. Tolia
Summary: Pfs25 is an important antigen for a malaria transmission-blocking vaccine, but its transmission-blocking activity and antibody potency decrease over time. This study provides a comprehensive definition of all transmission-reducing epitopes of Pfs25, using data from human antibody epitope mapping and crystal structures of Pfs25 in complex with transmission-reducing antibodies. These new structures reveal additional epitopes in Pfs25 that can reduce transmission and expand our understanding of malaria-exposed humans. This information can be used to design immunogens that specifically elicit antibodies against the transmission-reducing epitopes, leading to the development of more potent transmission-blocking vaccines for malaria.
Article
Multidisciplinary Sciences
Sylvie Georgette Zebaze Temgoua Kemleu, Laure Ngando, Elvige Nguekeng, Balotin Fogang, Marie Mafo Kapen, Styve Iruch Fopa, Marie Florence Biabi, Estelle Essangui, Jules Clement Assob Nguedia, Lawrence Ayong
Summary: The study highlights the utility of whole blood RT-LAMP for rapid screening of blood donors and suspected neonates, showing higher sensitivity compared to light microscopy and RDT.
Article
Immunology
Katharine A. Collins, Azrin N. Abd-Rahman, Louise Marquart, Emma Ballard, Nathalie Gobeau, Paul Griffin, Stephan Chalon, Joerg J. Moehrle, James S. McCarthy
Summary: This study evaluated the antimalarial activity of artefenomel, a new drug candidate, against P. vivax malaria. The results showed that artefenomel effectively cleared parasites after oral administration, but recrudescence occurred in some participants. The minimum inhibitory concentration and parasiticidal concentration were estimated, and a single 300-mg dose showed a high efficacy in clearing parasites. Gametocytemia was observed in all participants and cleared after dosing. Overall, the findings support further clinical development of artefenomel as a treatment for P. vivax malaria.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Review
Chemistry, Analytical
Hooi Tee Khoo, Chiuan Herng Leow
Summary: The article discusses the development of silica monolithic columns as an alternative approach to address the challenges of high back-pressure in HPLC systems. By utilizing smaller particle sizes and internal diameters, these columns have been widely investigated for fast and efficient separation of various molecules. The fabrication processes, derivatization, and endcapping techniques of the monolith are elaborated, along with highlighting the performance of such columns in key applications across different fields with various types of matrices.
Article
Medicine, Research & Experimental
Kayla Ann Andrews, Joel S. Owen, James McCarthy, David Wesche, Nathalie Gobeau, Thaddeus H. Grasela, Jorg J. Mohrle
Summary: Volunteer infection studies using IBSM model are effective for antimalarial drug development. Retrospective in silico analysis of previous data can improve study design and help establish PK/PD relationship early on, leading to rational dose selection for subsequent studies. A PK/PD model developed from initial data allows for accurate prediction of drug response in malaria infection.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2021)
Article
Infectious Diseases
Anand Odedra, Kari Mudie, Glen Kennedy, Rebecca E. Watts, Emilie Rossignol, Hayley Mitchell, Jeremy Gower, Maria Rebelo, Zuleima Pava, Rebecca Pawliw, Stephen Woolley, David G. Lalloo, Greg Robinson, Sean Lynch, Katharine A. Collins, Fiona Amante, James McCarthy
Summary: The study assessed the safety and effectiveness of using apheresis for extracting and concentrating P. vivax parasites, finding that apheresis can concentrate asexual parasites and gametocytes, but the concentration level is modest and may not be ideal for harvesting P. vivax.
Editorial Material
Medicine, General & Internal
Kirsty L. Buising, Deborah Williamson, Benjamin C. Cowie, Jennifer MacLachlan, Elizabeth Orr, Christopher MacIsaac, Eloise Williams, Katherine Bond, Stephen Muhi, James McCarthy, Andrea B. Maier, Louis Irving, Denise Heinjus, Cate Kelly, Caroline Marshall
MEDICAL JOURNAL OF AUSTRALIA
(2021)
Article
Biochemistry & Molecular Biology
Hui Ying Chong, Chiuan Yee Leow, Chiuan Herng Leow
Summary: The co-existence of JEV with highly homologous antigenic epitopes poses challenges in accurate serodiagnosis, leading to misdiagnosis and ineffective treatments. This study successfully generated soluble and active JEV NS1 protein through a cold-shocked E. coli expression system, providing a cost-effective alternative to mammalian or insect cell expression systems for JEV NS1 synthesis.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Chemistry, Medicinal
Musthahimah Muhamad, Chee-Yan Choo, Chiuan-Yee Leow
Summary: Cancer is a major cause of illness and death worldwide, with the Myrsinaceae family providing potential compounds with potent antitumor activity. Research on cytotoxic phytochemicals from this family offers insights into new directions and possibilities for cancer treatment.
JOURNAL OF BIOLOGICALLY ACTIVE PRODUCTS FROM NATURE
(2021)
Article
Biochemistry & Molecular Biology
Fauze Mahmud, Ngit Shin Lai, Siew Eng How, Jualang Azlan Gansau, Khairul Mohd Fadzli Mustaffa, Chiuan Herng Leow, Hasnah Osman, Hasidah Mohd Sidek, Noor Embi, Ping-Chin Lee
Summary: The study elucidates the inhibitory mechanisms of DBP against Hs GSK-3 beta and Pf 3D7, and the antimalarial mode of action of nocardamine. DBP inhibits Hs GSK-3 beta activity through binding to the substrate-binding site, while nocardamine inhibits Pf growth by chelating iron ions.
Review
Immunology
Che Muhammad Khairul Hisyam Bin Ismail, Nor Raihan Mohammad Shabani, Candy Chuah, Zurina Hassan, Abu Bakar Abdul Majeed, Chiuan Herng Leow, Kirnpal Kaur Banga Singh, Chiuan Yee Leow
Summary: This review summarizes the importance of iron-binding proteins in the survival and pathogenicity of the Shigella pathogen, as well as their potential use in vaccine and therapeutic development.
Article
Public, Environmental & Occupational Health
Chin Peng Lim, Boon Hui Kok, Hui Ting Lim, Candy Chuah, Badarulhisam Abdul Rahman, Abu Bakar Abdul Majeed, Michelle Wykes, Chiuan Herng Leow, Chiuan Yee Leow
Summary: Immunoinformatics plays a crucial role in accelerating vaccine research and development, especially in the design of vaccines targeting multiple variants of the coronavirus. It offers significant time and cost savings and enhances the reliability of results. Designing vaccines that effectively control the spread of the virus is of paramount importance in the current pandemic.
PATHOGENS AND GLOBAL HEALTH
(2023)
Article
Biochemistry & Molecular Biology
Nadya Panagides, Lucia F. Zacchi, Mitchell J. De Souza, Rodrigo A. Morales, Alexander Karnowski, Mark T. Liddament, Catherine M. Owczarek, Stephen M. Mahler, Con Panousis, Martina L. Jones, Christian Fercher
Summary: Monoclonal antibodies (mAbs) are highly successful and versatile protein-based pharmaceutical products used in the treatment of various pathological conditions. The quality and presentation format of the antigen play a crucial role in the selection outcomes of mAbs against membrane protein targets. Soluble presentation of a type I membrane protein is more advantageous in isolating functional mAbs with higher sequence diversity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Michael A. MacDonald, Matthias Nobel, Veronica S. Martinez, Kym Baker, Evan Shave, Peter P. Gray, Stephen Mahler, Trent Munro, Lars K. Nielsen, Esteban Marcellin
Summary: The development of death-resistant cell lines using CRISPR technology has proven to be beneficial for monoclonal antibody production. These cell lines showed advantages in fed-batch and perfusion bioreactors, with higher cell densities or longer culture durations in fed-batch, and the ability to culture without bleed in perfusion. This study highlights the potential of rationally engineered cell lines for improving mAb manufacturing processes.
Review
Immunology
Brent Brown, Vanshika Ojha, Ingo Fricke, Suhaila A. Al-Sheboul, Chinua Imarogbe, Tanya Gravier, Michael Green, Lori Peterson, Ivoyl P. Koutsaroff, Ayca Demir, Jonatane Andrieu, Chiuan Yee Leow, Chiuan Herng Leow
Summary: The COVID-19 pandemic is caused by the SARS-CoV-2 virus. The immune system plays a crucial role in fighting against viral infections. The development of single cell sequencing and other laboratory techniques provides valuable insights into immune cell characterization and autoimmune conditions.
Review
Virology
Maria Karolaynne da Silva, Daniel Melo de Oliveira Campos, Shopnil Akash, Shahina Akter, Leow Chiuan Yee, Umberto Laino Fulco, Jonas Ivan Nobre Oliveira
Summary: This article reviews the advances of reverse vaccinology in designing mRNA vaccines against SARS-CoV-2, discussing the steps, in silico tools, challenges, and future directions for improvement.