Article
Pharmacology & Pharmacy
Susan J. Keam
Summary: Concizumab is a subcutaneously administered humanised monoclonal IgG4 antibody developed by Novo Nordisk for the treatment of hemophilia A and B. It binds to the Kunitz-2 domain of tissue factor pathway inhibitor (TFPI) and prevents TFPI from binding to activated Factor X. In March 2023, it was approved in Canada for the treatment of adolescent and adult patients with hemophilia B who have FIX inhibitors and require routine prophylaxis to prevent or reduce the frequency of bleeding episodes.
Article
Biotechnology & Applied Microbiology
Hubert D. -J. Daniel, Sanjay Kumar, Rajesh Kannangai, Kavitha M. Lakshmi, Mavis Agbandje-Mckenna, Kirsten Coleman, Arun Srivastava, Alok Srivastava, Asha Mary Abraham
Summary: This study examined the levels of total antibodies and neutralizing antibodies (NAb) against AAV3 in healthy individuals and patients with hemophilia B in India. The prevalence of total antibodies and NAb was higher in patients with hemophilia B compared to healthy controls. These findings are important for determining the eligibility of patients for AAV vector-based gene therapy clinical trials.
HUMAN GENE THERAPY
(2021)
Article
Hematology
Nasim Shahidi Hamedani, Anouk Anna Marie Therese Donners, Matthijs van Luin, Simone Gasper, Heiko Ruehl, Claudia Klein, Thilo Albert, Mohsin EL Amrani, Bernd Poetzsch, Johannes Oldenburg, Jens Mueller
Summary: This study evaluated the impact of plasma FVIII activity on determining emicizumab levels and proposed different strategies for correcting or preanalytical inhibition of FVIII. The results showed that inhibitor-based FVIII neutralization is a feasible strategy for accurately measuring plasma emicizumab levels in the presence of FVIII activity.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Multidisciplinary Sciences
Pavlo Gilchuk, Isaac Thomsen, Sandra Yoder, Eric Brady, James D. Chappell, Laura J. Stevens, Mark R. Denison, Rachel E. Sutton, Rita E. Chen, Laura A. VanBlargan, Naveenchandra Suryadevara, Seth J. Zost, Jonathan Schmitz, Jill M. Pulley, Michael S. Diamond, Jillian P. Rhoads, Gordon R. Bernard, Wesley H. Self, Todd W. Rice, Allison P. Wheeler, James E. Crowe, Robert H. Carnahan
Summary: The COVID-19 pandemic has highlighted the urgent need for rapid evaluation of neutralizing antibody responses and the development of antibody-based treatments. The currently approved serological tests do not measure antibody-mediated viral neutralization, and there is a need for standardized quantitative neutralization assays. This study presents a high-throughput two-step profiling approach for identifying neutralizing convalescent plasma. Additionally, the researchers introduce a neutralizing antibody standard reagent to calibrate antibody neutralizing activity in convalescent plasma.
Article
Cell Biology
Alexandra C. Walls, Laura A. VanBlargan, Kai Wu, Angela Choi, Mary Jane Navarro, Diana Lee, Laura Avena, Daniela Montes Berrueta, Minh N. Pham, Sayda Elbashir, John C. Kraft, Marcos C. Miranda, Elizabeth Kepl, Max Johnson, Alyssa Blackstone, Kaitlin Sprouse, Brooke Fiala, Megan A. O'Connor, Natalie Brunette, Prabhu S. Arunachalam, Lisa Shirreff, Kenneth Rogers, Lauren Carter, Deborah H. Fuller, Francois Villinger, Bali Pulendran, Michael S. Diamond, Darin K. Edwards, Neil P. King, David Veesler
Summary: The use of BALB/c mice as an animal model to study neutralizing antibody responses against SARS-CoV-2 variants of concern (VOCs) may not accurately reflect the breadth and potency of responses observed in non-human primates or humans vaccinated with various vaccine platforms.
Article
Hematology
Eun-Young Kwak, Min Ju Kim, Jin Hyun Park, Ha Wook Jung, Myung Eun Jung
Summary: In this study, the correlation between PK and PD after administering MG1113 to monkeys was determined, and the PK and PD of MG1113 in humans were predicted using the results from monkeys. The study found that MG1113 showed nonlinear PK and a dose-response relationship with TFPI concentrations, which could be characterized using a TMDD model. These findings will be useful in designing the first-in-human study and establishing doses for further clinical trials.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Multidisciplinary Sciences
Prabhu S. Arunachalam, Alexandra C. Walls, Nadia Golden, Caroline Atyeo, Stephanie Fischinger, Chunfeng Li, Pyone Aye, Mary Jane Navarro, Lilin Lai, Venkata Viswanadh Edara, Katharina Roltgen, Kenneth Rogers, Lisa Shirreff, Douglas E. Ferrell, Samuel Wrenn, Deleah Pettie, John C. Kraft, Marcos C. Miranda, Elizabeth Kepl, Claire Sydeman, Natalie Brunette, Michael Murphy, Brooke Fiala, Lauren Carter, Alexander G. White, Meera Trisal, Ching-Lin Hsieh, Kasi Russell-Lodrigue, Christopher Monjure, Jason Dufour, Skye Spencer, Lara Doyle-Meyers, Rudolph P. Bohm, Nicholas J. Maness, Chad Roy, Jessica A. Plante, Kenneth S. Plante, Alex Zhu, Matthew J. Gorman, Sally Shin, Xiaoying Shen, Jane Fontenot, Shakti Gupta, Derek T. O'Hagan, Robbert Van Der Most, Rino Rappuoli, Robert L. Coffman, David Novack, Jason S. McLellan, Shankar Subramaniam, David Montefiori, Scott D. Boyd, JoAnne L. Flynn, Galit Alter, Francois Villinger, Harry Kleanthous, Jay Rappaport, Mehul S. Suthar, Neil P. King, David Veesler, Bali Pulendran
Summary: This study demonstrated the effectiveness of an adjuvanted RBD-NP vaccine in inducing robust and durable neutralizing antibody responses, providing protection against SARS-CoV-2 infection, and cross-neutralizing various variants. Adjuvants such as AS03 and AS37 significantly enhanced the immunogenicity of the vaccine and have the potential to be candidates for COVID-19 vaccines.
Article
Hematology
Carla Valsecchi, Marco Gobbi, Marten Beeg, Ty Adams, Giancarlo Castaman, Lucia Schiavone, James A. Huntington, Flora Peyvandi
Summary: The study characterized a neutralizing anti-emicizumab antibody in a pediatric hemophilia A patient with inhibitor, which was highly polyclonal with high-affinity binding mainly to the Fab portion of emicizumab and less binding to the Fc portion. This highlights the importance of close monitoring of neutralizing antibodies in patients with a history of poor drug efficacy.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Medicine, Research & Experimental
Durgesh Nadkarni, Jamie Lee, Qingping Jiang, Vimalkumar Patel, Verl Sriskanda, Kaushik Dutta, Debra M. Meyer
Summary: Antibody-drug conjugates (ADCs) are designed to target cancer cells specifically with cytotoxic drugs while minimizing systemic toxicity. The study found that the hydrophobicity of payloads and overall drug loading levels impact the in vitro target binding and cytotoxicity of ADC species.
MOLECULAR PHARMACEUTICS
(2021)
Article
Pharmacology & Pharmacy
Jean Donley, Darshana Jani, Tong Zhu, Yuhong Xiang, Boris Gorovits, Steven Arkin
Summary: Tissue factor pathway inhibitor (TFPI) is an endogenous inhibitor that can be inhibited to enhance the extrinsic coagulation pathway in patients with hemophilia. Marstacimab, a fully human monoclonal antibody, is being evaluated as a prophylactic treatment for severe hemophilia to reduce bleeding episodes. This study describes the evolution and validation of three electrochemiluminescence-based methods to detect marstacimab antidrug antibodies (ADAs) and confirms their value in monitoring ADA induction during treatment in hemophilia patients.
Article
Multidisciplinary Sciences
Young-Jun Park, Dora Pinto, Alexandra C. Walls, Zhuoming Liu, Anna De Marco, Fabio Benigni, Fabrizia Zatta, Chiara Silacci-Fregni, Jessica Bassi, Kaitlin R. Sprouse, Amin Addetia, John E. Bowen, Cameron Stewart, Martina Giurdanella, Christian Saliba, Barbara Guarino, Michael A. Schmid, Nicholas M. Franko, Jennifer K. Logue, Ha V. Dang, Kevin Hauser, Julia di Iulio, William Rivera, Gretja Schnell, Anushka Rajesh, Jiayi Zhou, Nisar Farhat, Hannah Kaiser, Martin Montiel-Ruiz, Julia Noack, Florian A. Lempp, Javier Janer, Rana Abdelnabi, Piet Maes, Paolo Ferrari, Alessandro Ceschi, Olivier Giannini, Guilherme Dias De Melo, Lauriane Kergoat, Herve Bourhy, Johan Neyts, Leah Soriaga, Lisa A. Purcell, Gyorgy Snell, Sean P. J. Whelan, Antonio Lanzavecchia, Herbert W. Virgin, Luca Piccoli, Helen Y. Chu, Matteo Samuele Pizzuto, Davide Corti, David Veesler
Summary: SARS-CoV-2 Omicron sublineages have spike mutations that allow them to evade antibodies from previous infection or vaccination. Hybrid immunity or booster shots can generate neutralizing antibodies against Omicron variants, and breakthrough infections lead to the production of neutralizing antibodies in the nasal mucosa. Antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases show cross-reactivity with different receptor-binding domains, while primary Omicron infections elicit B cells with narrow specificity. A highly potent pan-variant-neutralizing antibody has been identified as a potential candidate for clinical development.
Article
Virology
Linlin Zhai, Limin Zhang, Yushan Jiang, Baisheng Li, Minghui Yang, Khrustalev Vladislav Victorovich, Khrustaleva Tatyana Aleksandrovna, Mengjun Li, Yuelin Wang, Dong Huang, Zhujun Zeng, Zuning Ren, Hua Cao, Li Zhu, Qinghua Wu, Weiwei Xiao, Bao Zhang, Chengsong Wan, Fuxiang Wang, Ningshao Xia, Wei Zhao, Yixin Chen, Chenguang Shen
Summary: The discovery of broadly neutralizing monoclonal antibodies against influenza viruses has raised hope for new antiviral drugs. This study found that combinations of monoclonal antibodies targeting different antigenic epitopes against the influenza B virus showed stronger antiviral activity than single antibodies and other combinations. These antibody combinations also maintained good efficacy even when administration is delayed.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Immunology
Nesrin Gareayaghi, Mehmet Demirci, Dogukan Ozbey, Ferhat Dasdemir, Harika Oyku Dinc, Ilker Inanc Balkan, Suat Saribas, Nese Saltoglu, Bekir Kocazeybek
Summary: This study aimed to determine the levels of anti-S-RBD IgG antibodies and neutralizing antibody inhibition percentages (nAb IH%) formed after two doses of inactive or mRNA-based vaccine and a booster dose. The results showed that the heterologous booster dose led to a significant increase in both anti-S-RBD IgG levels and neutralizing antibodies. The study also found that the levels of binding and neutralizing antibodies were similar between those who received a heterologous booster dose and those who received a homologous booster dose, regardless of prior COVID-19 history.
Article
Immunology
Haijun Tang, Long Gao, Zhao Wu, Fang Meng, Xin Zhao, Yun Shao, Guocun Hou, Xiaohong Du, F. Xiao-Feng Qin
Summary: The emergence of SARS-CoV-2 variants, especially the variants of concern, has worsened the impact of the COVID-19 pandemic. Mutations in the spike protein of the variants have the potential to alter the infectivity and antigenicity of SARS-CoV-2, allowing it to evade neutralizing antibodies. This study assessed the mutations in the spike protein of newly emerging variants and found significant changes in viral infectivity. Certain variants were able to infect less susceptible cells and complete the infection process in a shorter time. Neutralizing antibodies and vaccinated sera partially or completely failed to inhibit host cell entry mediated by the spike protein of certain variants. However, protease inhibitors and endocytosis inhibitors were still effective in blocking viral infection mediated by the variant spike proteins.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Susan Pederson, David M. Biondi, Brent Allan, Roger Cady, Barbara Schaeffler, Brian Baker, John Latham
Summary: Across five clinical trials, the immunogenicity of eptinezumab was characterized by low titer and transient ADA and NAb responses, with no clinically meaningful impact on efficacy and safety profiles. The onset of detectable ADA occurred at week 8, peaked at week 24, and declined steadily thereafter, regardless of eptinezumab dose level or number of doses.
FRONTIERS IN IMMUNOLOGY
(2021)
