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Science of biotechnology – Monoclonal antibody technology
Published in Ronald P. Evens, Biotechnology, 2020
An alternative mode of development for monoclonal antibodies is antibody “phage” display (APD), which has been used in 5 of the 86 mab molecules currently marketed (adalimumab, belimumab, necitumumab, ramucirumab, raxibacumab). In APD, mabs are fully developed in the test tube, based on the physical link between function (antigen binding of mabs) and information (mab genes) in nanoparticle phages (viruses that infect bacteria, such as Escherichia coli). The high antigen affinity and high specificity of mabs to their antigen allows APD to create the specific mab for the specific antigen of a disease. Four main elements are required, that is, (1) preparation of human antibody gene libraries containing millions of mab genes, (2) genetic engineering of bacteriophages to bind mabs [the antigen-binding fragment (Fab) or single-chain variable fragment (scFv) segments of a mab] and serve as probes to filter out mabs against desired antigen targets, (3) serial panning of the gene libraries with the bacteriophage-mab probes, (4) analysis of mab clones. Then, the manufacture of mabs by recombinant DNA methods can ensue. An advantage of this APD system is that the mabs are fully human. A limit to this set of procedures is the laborious nature of the process.
Anthrax
Published in Meera Chand, John Holton, Case Studies in Infection Control, 2018
In this case, extensive soft tissue debridement was performed in the operating theatre and high-dose antibiotics (benzylpenicillin 1.2 g every four hours and clindamycin 600 mg every six hours) were commenced. The patient made a good recovery following debridement. Other potential therapies, such as human anthrax immunoglobulin (used to eliminate circulating toxins) and Raxibacumab (a human IgG1 monoclonal antibody directed at the protective antigen of B. anthracis), were considered but not used.
Anthrax prevention through vaccine and post-exposure therapy
Published in Expert Opinion on Biological Therapy, 2020
Manish Manish, Shashikala Verma, Divya Kandari, Parul Kulshreshtha, Samer Singh, Rakesh Bhatnagar
Antitoxin antibodies are recommended in conjunction with antibiotics in case of systemic human infections. Two monoclonal antibodies (mAb), namely, 3B6 and 14B7 among a panel of 36 were identified to be able to effectively neutralize LT and ET by blocking the interaction of PA with cells [36]. Both mAbs 3B6 and 14B7 were found to bind to the same epitope of PA. The epitope for mAb 14B7 comprised residues 682, 684, 685, 686, 687, and 688 [37], which are part of one of the loops of PA that is required for its interaction with ATRs. This loop is also targeted by mAb, 35PA83 – a macaque-derived Ab that neutralizes LT [38]. The murine mAbs 1-F1 and 2-B12 recognized epitopes are also found to be adjacent to the loop recognized by 14B7 [39]. Moreover, chimpanzee mAbs such as W1 and W2 which prevent the binding of PA to cells recognized three of the four loops of PA involved in its interaction with ATRs [40]. Currently, three antitoxin antibodies that target PA are approved by the FDA for inhalational anthrax, namely Raxibacumab, obiltoxaximab/Anthim®/ETI-204 [41,42], and polyclonal Anthrax Immunoglobulin-IV or ANTHRASIL. The antibody Raxibacumab is a recombinant human IgG1 derived from 14B7 [43], the Obiltoxaximab/ETI-204 is a chimeric IgG1 monoclonal Ab derived from 14B7 containing human constant region sequences and deimmunized murine variable region [44], while the ANTHRASIL is a polyclonal formulation prepared by purifying IgG fraction of antibodies from the plasma of healthy donors immunized with AVA or BioThrax® [45]. However, it should be noted that the inability of antitoxin antibodies to cross the blood-brain barrier (BBB) drastically reduces their protective efficacy with the delay in post-exposure administration as meningitis may have already developed [33,46,47]. Nevertheless, the development of engineered antibodies for BBB-crossing function and alternatively the engineered cell-derived BBB targeted nanovesicles or exosomes hold promise to overcome this hurdle and further increase their utility [48].