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      Recombinant snakebite antivenoms: A cost-competitive solution to a neglected tropical disease?

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          Abstract

          Snakebite envenoming is a major public health burden in tropical parts of the developing world. In sub-Saharan Africa, neglect has led to a scarcity of antivenoms threatening the lives and limbs of snakebite victims. Technological advances within antivenom are warranted, but should be evaluated not only on their possible therapeutic impact, but also on their cost-competitiveness. Recombinant antivenoms based on oligoclonal mixtures of human IgG antibodies produced by CHO cell cultivation may be the key to obtaining better snakebite envenoming therapies. Based on industry data, the cost of treatment for a snakebite envenoming with a recombinant antivenom is estimated to be in the range USD 60–250 for the Final Drug Product. One of the effective antivenoms (SAIMR Snake Polyvalent Antivenom from the South African Vaccine Producers) currently on the market has been reported to have a wholesale price of USD 640 per treatment for an average snakebite. Recombinant antivenoms may therefore in the future be a cost-competitive alternative to existing serum-based antivenoms.

          Author summary

          Given the medical importance of snakebite envenoming and the current shortage of antivenoms in sub-Saharan Africa, technological advances in antivenom development and production are needed. One of the avenues that could be taken involves the use of recombinant antivenoms based on oligoclonal mixtures of human IgG antibodies, since these may have the benefits of being compatible with the human immune system and their production is independent on animal immune systems and venom procurement. However, an important aspect of introducing recombinant antivenoms to the clinic is their cost of production given that snakebite victims are often poor rural workers living in remote parts of the tropical parts of the developing world. Here, we aim to provide cost estimates of recombinant antivenom manufacture with special focus on snakebite envenoming in sub-Saharan Africa. Our results indicate that recombinant antivenoms in the future will indeed be cost-competitive compared to existing animal-derived serum-based antivenoms. Furthermore, we outline different manufacturing strategies and suggest the use of caprylic acid precipitation as a low cost purification method following cultivation of CHO cells for antibody expression due to its use in current antivenom manufacture.

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          Most cited references26

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          Snake-bites: appraisal of the global situation.

          J Chippaux (1998)
          The true global incidence of envenomations and their severity remain largely misunderstood, except for a few countries where these accidents are rare or are correctly reported. Nevertheless, this information is essential for drawing up guidelines for dealing with snake-bites, to plan drug supplies, particularly antivenin, and to train medical staff on snake-bite treatments. Since the comprehensive review by Swaroop & Grab in 1954 no global survey has been carried out on snake-bite epidemiology. The present article is an attempt to draw the attention of health authorities to snake envenomations and urges them to prepare therapeutic protocols adapted to their needs.
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            Therapeutic antibodies for autoimmunity and inflammation.

            The development of therapeutic antibodies has evolved over the past decade into a mainstay of therapeutic options for patients with autoimmune and inflammatory diseases. Substantial advances in understanding the biology of human diseases have been made and tremendous benefit to patients has been gained with the first generation of therapeutic antibodies. The lessons learnt from these antibodies have provided the foundation for the discovery and development of future therapeutic antibodies. Here we review how key insights obtained from the development of therapeutic antibodies complemented by newer antibody engineering technologies are delivering a second generation of therapeutic antibodies with promise for greater clinical efficacy and safety.
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              Biopharmaceutical benchmarks 2014.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                3 February 2017
                February 2017
                : 11
                : 2
                : e0005361
                Affiliations
                [1 ]Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
                [2 ]National Veterinary Institute, Technical University of Denmark, Kongens Lyngby, Denmark
                [3 ]Department of Bio and Health Informatics, Technical University of Denmark, Kongens Lyngby, Denmark
                Liverpool School of Tropical Medicine, UNITED KINGDOM
                Author notes

                The authors have declared that no competing interests exist.

                • Conceptualization: AHL.

                • Formal analysis: AHL KHJ.

                • Funding acquisition: AHL ME.

                • Investigation: AHL KHJ.

                • Methodology: AHL KHJ ME MRA.

                • Project administration: AHL.

                • Supervision: AHL MRA.

                • Validation: AHL KHJ ME MRA.

                • Visualization: AHL KHJ ME.

                • Writing – original draft: AHL KHJ.

                • Writing – review & editing: AHL KHJ ME MRA.

                Author information
                http://orcid.org/0000-0001-6918-5574
                Article
                PNTD-D-16-01921
                10.1371/journal.pntd.0005361
                5310919
                28158193
                1596d173-eecf-47f0-85f0-af9a63ad523e
                © 2017 Laustsen et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 20 October 2016
                : 27 January 2017
                Page count
                Figures: 5, Tables: 0, Pages: 14
                Funding
                Funded by: Novo Nordisk Foundation
                Award ID: NNF13OC0005613
                Award Recipient :
                Funded by: Novo Nordisk Foundation
                Award ID: NNF16OC0019248
                Award Recipient :
                This work was supported by NNF13OC0005613 (ME) and NNF16OC0019248 (AHL) received from the Novo Nordisk Foundation ( http://novonordiskfonden.dk/da). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Tropical Diseases
                Neglected Tropical Diseases
                Snakebite
                Research and Analysis Methods
                Immunologic Techniques
                Antibody Production
                Biology and Life Sciences
                Physiology
                Immune Physiology
                Antibodies
                Medicine and Health Sciences
                Physiology
                Immune Physiology
                Antibodies
                Biology and Life Sciences
                Immunology
                Immune System Proteins
                Antibodies
                Medicine and Health Sciences
                Immunology
                Immune System Proteins
                Antibodies
                Biology and Life Sciences
                Biochemistry
                Proteins
                Immune System Proteins
                Antibodies
                Biology and Life Sciences
                Organisms
                Animals
                Vertebrates
                Amniotes
                Reptiles
                Squamates
                Snakes
                Biology and Life Sciences
                Toxicology
                Toxic Agents
                Toxins
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Toxicology
                Toxic Agents
                Toxins
                Biology and Life Sciences
                Toxicology
                Toxic Agents
                Toxins
                Venoms
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Toxicology
                Toxic Agents
                Toxins
                Venoms
                Research and Analysis Methods
                Precipitation Techniques
                Research and analysis methods
                Biological cultures
                Cell lines
                CHO cells
                Custom metadata
                vor-update-to-uncorrected-proof
                2017-02-15
                All relevant data are within the paper and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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