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Dr. Andreas Laustsen
Department of Biotechnology and Biomedicine, Technical University of Denmark, 2800 Kongens Lyngby, Denmark

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Research Keywords & Expertise

0 Biologics
0 Biotherapeutics
0 Infectious Diseases
0 Phage Display
0 Snakebite envenoming

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Snakebite envenoming
Phage Display
Next-generation antivenoms
Recombinant antivenom
Antibody discovery
Toxicovenomics
Toxin synergism
Antibody technologies
Biotherapeutics
Infectious Diseases
Biologics
Toxin neutralization

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Journal article
Published: 08 August 2021 in Toxicon: X
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Snakebite envenoming is a major cause of morbidity and mortality in rural communities throughout the tropics. Generally, the main clinical features of snakebites are local swelling, tissue necrosis, shock, spontaneous systemic hemorrhage, incoagulable blood, paralysis, rhabdomyolysis, and acute kidney injury. These clinical manifestations result from complex biochemical venom constituents comprising of cytotoxins, hemotoxins, neurotoxins, myotoxins, and other substances. Timely diagnosis of envenoming and identification of the responsible snake species is clinically challenging in many parts of the world and necessitates prompt and thorough clinical assessment, which could be supported by the development of reliable, affordable, widely-accessible, point-of-care tests. Conventional antivenoms based on polyclonal antibodies derived from animals remain the mainstay of therapy along with supportive medical and surgical care. However, while antivenoms save countless lives, they are associated with adverse reactions, limited potency, and are relatively inefficacious against presynaptic neurotoxicity and in preventing necrosis. Nevertheless, major scientific and technological advances are facilitating the development of new molecular and immunologic diagnostic tests, as well as a new generation of antivenoms comprising human monoclonal antibodies with broader and more potent neutralization capacity and less immunogenicity. Repurposed pharmaceuticals based on small molecule inhibitors (e.g., marimastat and varespladib) used alone and in combination against enzymatic toxins, such as metalloproteases and phospholipase A2s, have shown promise in animal studies. These orally bioavailable molecules could serve as early interventions in the out-of-hospital setting if confirmed to be safe and efficacious in clinical studies. Antivenom access can be improved by the usage of drones and ensuring constant antivenom supply in remote endemic rural areas. Overall, the improvement of clinical management of snakebite envenoming requires sustained, coordinated, and multifaceted efforts involving basic and applied sciences, new technology, product development, effective clinical training, implementation of existing guidelines and therapeutic approaches, supported by improved supply of existing antivenoms.

ACS Style

Muhammad Hamza; Cecilie Knudsen; Christeine Ariaranee Gnanathasan; Wuelton Monteiro; Matthew R. Lewin; Andreas H. Laustsen; Abdulrazaq G. Habib. Clinical management of snakebite envenoming: Future perspectives. Toxicon: X 2021, 11, 100079 .

AMA Style

Muhammad Hamza, Cecilie Knudsen, Christeine Ariaranee Gnanathasan, Wuelton Monteiro, Matthew R. Lewin, Andreas H. Laustsen, Abdulrazaq G. Habib. Clinical management of snakebite envenoming: Future perspectives. Toxicon: X. 2021; 11 ():100079.

Chicago/Turabian Style

Muhammad Hamza; Cecilie Knudsen; Christeine Ariaranee Gnanathasan; Wuelton Monteiro; Matthew R. Lewin; Andreas H. Laustsen; Abdulrazaq G. Habib. 2021. "Clinical management of snakebite envenoming: Future perspectives." Toxicon: X 11, no. : 100079.

Opinion
Published: 25 March 2021 in Trends in Biotechnology
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For years, a discussion has persevered on the benefits and drawbacks of antibody discovery using animal immunization versus in vitro selection from non-animal-derived recombinant repertoires using display technologies. While it has been argued that using recombinant display libraries can reduce animal consumption, we hold that the number of animals used in immunization campaigns is dwarfed by the number sacrificed during preclinical studies. Thus, improving quality control of antibodies before entering in vivo studies will have a larger impact on animal consumption. Both animal immunization and recombinant repertoires present unique advantages for discovering antibodies that are fit for purpose. Furthermore, we anticipate that machine learning will play a significant role within discovery workflows, refining current antibody discovery practices.

ACS Style

Andreas H. Laustsen; Victor Greiff; Aneesh Karatt-Vellatt; Serge Muyldermans; Timothy P. Jenkins. Animal Immunization, in Vitro Display Technologies, and Machine Learning for Antibody Discovery. Trends in Biotechnology 2021, 1 .

AMA Style

Andreas H. Laustsen, Victor Greiff, Aneesh Karatt-Vellatt, Serge Muyldermans, Timothy P. Jenkins. Animal Immunization, in Vitro Display Technologies, and Machine Learning for Antibody Discovery. Trends in Biotechnology. 2021; ():1.

Chicago/Turabian Style

Andreas H. Laustsen; Victor Greiff; Aneesh Karatt-Vellatt; Serge Muyldermans; Timothy P. Jenkins. 2021. "Animal Immunization, in Vitro Display Technologies, and Machine Learning for Antibody Discovery." Trends in Biotechnology , no. : 1.

Immunology
Published: 12 November 2020 in Frontiers in Immunology
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Widow spiders are among the few spider species worldwide that can cause serious envenoming in humans. The clinical syndrome resulting from Latrodectus spp. envenoming is called latrodectism and characterized by pain (local or regional) associated with diaphoresis and nonspecific systemic effects. The syndrome is caused by α-latrotoxin, a ~130 kDa neurotoxin that induces massive neurotransmitter release. Due to this function, α-latrotoxin has played a fundamental role as a tool in the study of neuroexocytosis. Nevertheless, some questions concerning its mode of action remain unresolved today. The diagnosis of latrodectism is purely clinical, combined with the patient’s history of spider bite, as no analytical assays exist to detect widow spider venom. By utilizing antibody phage display technology, we here report the discovery of the first recombinant human monoclonal immunoglobulin G antibody (TPL0020_02_G9) that binds α-latrotoxin from the Mediterranean black widow spider (Latrodectus tredecimguttatus) and show neutralization efficacy ex vivo. Such antibody can be used as an affinity reagent for research and diagnostic purposes, providing researchers with a novel tool for more sophisticated experimentation and analysis. Moreover, it may also find therapeutic application in future.

ACS Style

Sofie Føns; Line Ledsgaard; Maxim V. Nikolaev; Alexander A. Vassilevski; Christoffer V. Sørensen; Manon K. Chevalier; Michael Fiebig; Andreas H. Laustsen. Discovery of a Recombinant Human Monoclonal Immunoglobulin G Antibody Against α-Latrotoxin From the Mediterranean Black Widow Spider (Latrodectus tredecimguttatus). Frontiers in Immunology 2020, 11, 1 .

AMA Style

Sofie Føns, Line Ledsgaard, Maxim V. Nikolaev, Alexander A. Vassilevski, Christoffer V. Sørensen, Manon K. Chevalier, Michael Fiebig, Andreas H. Laustsen. Discovery of a Recombinant Human Monoclonal Immunoglobulin G Antibody Against α-Latrotoxin From the Mediterranean Black Widow Spider (Latrodectus tredecimguttatus). Frontiers in Immunology. 2020; 11 ():1.

Chicago/Turabian Style

Sofie Føns; Line Ledsgaard; Maxim V. Nikolaev; Alexander A. Vassilevski; Christoffer V. Sørensen; Manon K. Chevalier; Michael Fiebig; Andreas H. Laustsen. 2020. "Discovery of a Recombinant Human Monoclonal Immunoglobulin G Antibody Against α-Latrotoxin From the Mediterranean Black Widow Spider (Latrodectus tredecimguttatus)." Frontiers in Immunology 11, no. : 1.

Review
Published: 22 October 2020 in Toxins
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Snake ‘dry bites’ are characterized by the absence of venom being injected into the victim during a snakebite incident. The dry bite mechanism and diagnosis are quite complex, and the lack of envenoming symptoms in these cases may be misinterpreted as a miraculous treatment or as proof that the bite from the perpetrating snake species is rather harmless. The circumstances of dry bites and their clinical diagnosis are not well-explored in the literature, which may lead to ambiguity amongst treating personnel about whether antivenom is indicated or not. Here, the epidemiology and recorded history of dry bites are reviewed, and the clinical knowledge on the dry bite phenomenon is presented and discussed. Finally, this review proposes a diagnostic and therapeutic protocol to assist medical care after snake dry bites, aiming to improve patient outcomes.

ACS Style

Manuela B. Pucca; Cecilie Knudsen; Isadora S. Oliveira; Charlotte Rimbault; Felipe A. Cerni; Fan Hui Wen; Jacqueline Sachett; Marco A. Sartim; Andreas H. Laustsen; Wuelton M. Monteiro. Current Knowledge on Snake Dry Bites. Toxins 2020, 12, 668 .

AMA Style

Manuela B. Pucca, Cecilie Knudsen, Isadora S. Oliveira, Charlotte Rimbault, Felipe A. Cerni, Fan Hui Wen, Jacqueline Sachett, Marco A. Sartim, Andreas H. Laustsen, Wuelton M. Monteiro. Current Knowledge on Snake Dry Bites. Toxins. 2020; 12 (11):668.

Chicago/Turabian Style

Manuela B. Pucca; Cecilie Knudsen; Isadora S. Oliveira; Charlotte Rimbault; Felipe A. Cerni; Fan Hui Wen; Jacqueline Sachett; Marco A. Sartim; Andreas H. Laustsen; Wuelton M. Monteiro. 2020. "Current Knowledge on Snake Dry Bites." Toxins 12, no. 11: 668.

Communication
Published: 19 August 2020 in Toxins
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In the field of antivenom research, development, and manufacture, it is often advised to follow the World Health Organization’s (WHO) guidelines for the production, control, and regulation of snake antivenom immunoglobulins, which recommend the use of preincubation assays to assess the efficacy of snakebite therapeutics. In these assays, venom and antivenom are mixed and incubated prior to in vivo administration to rodents, which allows for a standardizable comparison of antivenoms with similar characteristics. However, these assays are not necessarily sufficient for therapeutics with significantly different pharmacological properties than antibody-based antivenoms, such as small molecule inhibitors, nanoparticles, and other modalities. To ensure that the in vivo therapeutic utility of completely novel toxin-neutralizing molecules with no history of use in envenoming therapy and variable pharmacokinetics is properly evaluated, such molecules must also be tested in preclinical rescue assays, where rodents are first challenged with appropriate doses of venoms or toxins, followed by the administration of neutralizing modalities after an appropriate time delay to better mimic the real-life scenarios faced by human snakebite victims. Such an approach takes the venom (or toxin) toxicokinetics, the drug pharmacokinetics, and the drug pharmacodynamics into consideration. If new modalities are only assessed in preincubation assays and not subjected to evaluation in rescue assays, the publication of neutralization data may unintentionally misrepresent the actual therapeutic efficacy and suitability of the modality being tested, and thus potentially misguide strategic decision making in the research and development of novel therapies for snakebite envenoming.

ACS Style

Cecilie Knudsen; Nicholas Casewell; Bruno Lomonte; José Gutiérrez; Sakthivel Vaiyapuri; Andreas Laustsen. Novel Snakebite Therapeutics Must Be Tested in Appropriate Rescue Models to Robustly Assess Their Preclinical Efficacy. Toxins 2020, 12, 528 .

AMA Style

Cecilie Knudsen, Nicholas Casewell, Bruno Lomonte, José Gutiérrez, Sakthivel Vaiyapuri, Andreas Laustsen. Novel Snakebite Therapeutics Must Be Tested in Appropriate Rescue Models to Robustly Assess Their Preclinical Efficacy. Toxins. 2020; 12 (9):528.

Chicago/Turabian Style

Cecilie Knudsen; Nicholas Casewell; Bruno Lomonte; José Gutiérrez; Sakthivel Vaiyapuri; Andreas Laustsen. 2020. "Novel Snakebite Therapeutics Must Be Tested in Appropriate Rescue Models to Robustly Assess Their Preclinical Efficacy." Toxins 12, no. 9: 528.

Original research article
Published: 10 July 2020 in Frontiers in Bioengineering and Biotechnology
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Snakebite envenoming is a neglected tropical disease that affects millions of people across the globe. It has been suggested that recombinant antivenoms based on mixtures of human monoclonal antibodies, which target key toxins of medically important snake venom, could present a promising avenue toward the reduction of morbidity and mortality of envenomated patients. However, since snakebite envenoming is a disease of poverty, it is pivotal that next-generation therapies are affordable to those most in need; this warrants analysis of the cost dynamics of recombinant antivenom manufacture. Therefore, we present, for the first time, a bottom-up analysis of the cost dynamics surrounding the production of future recombinant antivenoms based on available industry data. We unravel the potential impact that venom volume, abundance of medically relevant toxins in a venom, and the molecular weight of these toxins may have on the final product cost. Furthermore, we assess the roles that antibody molar mass, manufacturing and purification strategies, formulation, antibody efficacy, and potential cross-reactivity play in the complex cost dynamics of recombinant antivenom manufacture. Notably, according to our calculations, it appears that such next-generation antivenoms based on cocktails of monoclonal immunoglobulin Gs (IgGs) could be manufacturable at a comparable or lower cost to current plasma-derived antivenoms, which are priced at USD 13-1120 per treatment. We found that monovalent recombinant antivenoms based on IgGs could be manufactured for USD 20-225 per treatment, while more complex polyvalent recombinant antivenoms based on IgGs could be manufactured for USD 48-1354 per treatment. Finally, we investigated the prospective cost of manufacturing for recombinant antivenoms based on alternative protein scaffolds, such as DARPins and nanobodies, and highlight the potential utility of such scaffolds in the context of low-cost manufacturing. In conclusion, the development of recombinant antivenoms not only holds a promise for improving therapeutic parameters, such as safety and efficacy, but could possibly also lead to a more competetive cost of manufacture of antivenom products for patients worldwide.

ACS Style

Timothy P. Jenkins; Andreas Hougaard Laustsen. Cost of Manufacturing for Recombinant Snakebite Antivenoms. Frontiers in Bioengineering and Biotechnology 2020, 8, 703 .

AMA Style

Timothy P. Jenkins, Andreas Hougaard Laustsen. Cost of Manufacturing for Recombinant Snakebite Antivenoms. Frontiers in Bioengineering and Biotechnology. 2020; 8 ():703.

Chicago/Turabian Style

Timothy P. Jenkins; Andreas Hougaard Laustsen. 2020. "Cost of Manufacturing for Recombinant Snakebite Antivenoms." Frontiers in Bioengineering and Biotechnology 8, no. : 703.

Journal article
Published: 01 July 2020 in Scientific Reports
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Broadly-neutralizing monoclonal antibodies are of high therapeutic utility against infectious diseases caused by bacteria and viruses, as well as different types of intoxications. Snakebite envenoming is one such debilitating pathology, which is currently treated with polyclonal antibodies derived from immunized animals. For the development of novel envenoming therapies based on monoclonal antibodies with improved therapeutic benefits, new discovery approaches for broadly-neutralizing antibodies are needed. Here, we present a methodology based on phage display technology and a cross-panning strategy that enables the selection of cross-reactive monoclonal antibodies that can broadly neutralize toxins from different snake species. This simple in vitro methodology is immediately useful for the development of broadly-neutralizing (polyvalent) recombinant antivenoms with broad species coverage, but may also find application in the development of broadly-neutralizing antibodies against bacterial, viral, and parasitic agents that are known for evading therapy via resistance mechanisms and antigen variation.

ACS Style

Shirin Ahmadi; Manuela B. Pucca; Jonas A. Jürgensen; Rahel Janke; Line Ledsgaard; Erwin M. Schoof; Christoffer V. Sørensen; Figen Çalışkan; Andreas H. Laustsen. An in vitro methodology for discovering broadly-neutralizing monoclonal antibodies. Scientific Reports 2020, 10, 1 -7.

AMA Style

Shirin Ahmadi, Manuela B. Pucca, Jonas A. Jürgensen, Rahel Janke, Line Ledsgaard, Erwin M. Schoof, Christoffer V. Sørensen, Figen Çalışkan, Andreas H. Laustsen. An in vitro methodology for discovering broadly-neutralizing monoclonal antibodies. Scientific Reports. 2020; 10 (1):1-7.

Chicago/Turabian Style

Shirin Ahmadi; Manuela B. Pucca; Jonas A. Jürgensen; Rahel Janke; Line Ledsgaard; Erwin M. Schoof; Christoffer V. Sørensen; Figen Çalışkan; Andreas H. Laustsen. 2020. "An in vitro methodology for discovering broadly-neutralizing monoclonal antibodies." Scientific Reports 10, no. 1: 1-7.

Research article
Published: 24 June 2020 in PLOS Neglected Tropical Diseases
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Snakebite envenoming is a major neglected tropical disease that affects millions of people every year. The only effective treatment against snakebite envenoming consists of unspecified cocktails of polyclonal antibodies purified from the plasma of immunized production animals. Currently, little data exists on the molecular interactions between venom-toxin epitopes and antivenom-antibody paratopes. To address this issue, high-density peptide microarray (hdpm) technology has recently been adapted to the field of toxinology. However, analysis of such valuable datasets requires expert understanding and, thus, complicates its broad application within the field. In the present study, we developed a user-friendly, and high-throughput web application named “Snake Toxin and Antivenom Binding Profiles” (STAB Profiles), to allow straight-forward analysis of hdpm datasets. To test our tool and evaluate its performance with a large dataset, we conducted hdpm assays using all African snake toxin protein sequences available in the UniProt database at the time of study design, together with eight commercial antivenoms in clinical use in Africa, thus representing the largest venom-antivenom dataset to date. Furthermore, we introduced a novel method for evaluating raw signals from a peptide microarray experiment and a data normalization protocol enabling intra-microarray and even inter-microarray chip comparisons. Finally, these data, alongside all the data from previous similar studies by Engmark et al., were preprocessed according to our newly developed protocol and made publicly available for download through the STAB Profiles web application (http://tropicalpharmacology.com/tools/stab-profiles/). With these data and our tool, we were able to gain key insights into toxin-antivenom interactions and were able to differentiate the ability of different antivenoms to interact with certain toxins of interest. The data, as well as the web application, we present in this article should be of significant value to the venom-antivenom research community. Knowledge gained from our current and future analyses of this dataset carry the potential to guide the improvement and optimization of current antivenoms for maximum patient benefit, as well as aid the development of next-generation antivenoms. Millions of people are bitten by venomous snakes each year, resulting in over 100,000 deaths. Currently, such envenomings are treated with animal derived antivenoms that contain undefined antibodies against snake venom toxins that have been raised by the production animal’s immune system. To date, our understanding of these antibody toxin interactions is sparse, but with the help of high-density peptide microarray (hdpm) technology this is starting to change. Whilst this technology is very powerful, analysis of the output data is complex and requires expert training. Therefore, in this study, we developed a user-friendly, and high-throughput web application named “Snake Toxin and Antivenom Binding Profiles” (STAB Profiles). Furthermore, we ensured our tool was functional and able to handle large amounts of data by creating an entirely novel and larger than ever hdpm dataset based on all African snake toxin proteins together with eight commercial antivenoms. With these data and our tool, we were able to further our understanding on toxin-antivenom interactions and were able to differentiate the ability of different antivenoms to interact with certain toxins of interest. Ideally, these and future insights can help guide the improvement and optimization of current antivenoms, as well as aid the informed development of next-generation antivenoms.

ACS Style

Kamille E. Krause; Timothy P. Jenkins; Carina Skaarup; Mikael Engmark; Nicholas R. Casewell; Stuart Ainsworth; Bruno Lomonte; Julián Fernández; José M. Gutiérrez; Ole Lund; Andreas H. Laustsen. An interactive database for the investigation of high-density peptide microarray guided interaction patterns and antivenom cross-reactivity. PLOS Neglected Tropical Diseases 2020, 14, e0008366 .

AMA Style

Kamille E. Krause, Timothy P. Jenkins, Carina Skaarup, Mikael Engmark, Nicholas R. Casewell, Stuart Ainsworth, Bruno Lomonte, Julián Fernández, José M. Gutiérrez, Ole Lund, Andreas H. Laustsen. An interactive database for the investigation of high-density peptide microarray guided interaction patterns and antivenom cross-reactivity. PLOS Neglected Tropical Diseases. 2020; 14 (6):e0008366.

Chicago/Turabian Style

Kamille E. Krause; Timothy P. Jenkins; Carina Skaarup; Mikael Engmark; Nicholas R. Casewell; Stuart Ainsworth; Bruno Lomonte; Julián Fernández; José M. Gutiérrez; Ole Lund; Andreas H. Laustsen. 2020. "An interactive database for the investigation of high-density peptide microarray guided interaction patterns and antivenom cross-reactivity." PLOS Neglected Tropical Diseases 14, no. 6: e0008366.

Review
Published: 19 June 2020 in Trends in Pharmacological Sciences
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Snake venoms are mixtures of toxins that vary extensively between and within snake species. This variability has serious consequences for the management of the world's 1.8 million annual snakebite victims. Advances in ‘omic' technologies have empowered toxinologists to comprehensively characterize snake venom compositions, unravel the molecular mechanisms that underpin venom variation, and elucidate the ensuing functional consequences. In this review, we describe how such mechanistic processes have resulted in suites of toxin isoforms that cause diverse pathologies in human snakebite victims and we detail how variation in venom composition can result in treatment failure. Finally, we outline current therapeutic approaches designed to circumvent venom variation and deliver next-generation treatments for the world's most lethal neglected tropical disease.

ACS Style

Nicholas R. Casewell; Timothy N.W. Jackson; Andreas Hougaard Laustsen; Kartik Sunagar. Causes and Consequences of Snake Venom Variation. Trends in Pharmacological Sciences 2020, 41, 570 -581.

AMA Style

Nicholas R. Casewell, Timothy N.W. Jackson, Andreas Hougaard Laustsen, Kartik Sunagar. Causes and Consequences of Snake Venom Variation. Trends in Pharmacological Sciences. 2020; 41 (8):570-581.

Chicago/Turabian Style

Nicholas R. Casewell; Timothy N.W. Jackson; Andreas Hougaard Laustsen; Kartik Sunagar. 2020. "Causes and Consequences of Snake Venom Variation." Trends in Pharmacological Sciences 41, no. 8: 570-581.

Short communication
Published: 04 June 2020 in Toxicon
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Bushmasters (Lachesis spp) and lancehead vipers (Bothrops spp) are two of the most dangerous snakes found in Latin America. Victims of envenoming by these snakes require urgent administration of antivenom. Here, we report the identification of a small set of broadly neutralizing human monoclonal single-chain variable fragment (scFv) antibodies targeting key phospholipases A2 from Lachesis and Bothrops spp using phage display technology and demonstrate their in vitro efficacy using a hemolysis assay.

ACS Style

Lucas B. Campos; Manuela B. Pucca; Luciano C. Silva; Gabriela Pessenda; Bruno A. Filardi; Felipe A. Cerni; Isadora S. Oliveira; Andreas H. Laustsen; Eliane C. Arantes; José E. Barbosa. Identification of cross-reactive human single-chain variable fragments against phospholipases A2 from Lachesis muta and Bothrops spp venoms. Toxicon 2020, 184, 116 -121.

AMA Style

Lucas B. Campos, Manuela B. Pucca, Luciano C. Silva, Gabriela Pessenda, Bruno A. Filardi, Felipe A. Cerni, Isadora S. Oliveira, Andreas H. Laustsen, Eliane C. Arantes, José E. Barbosa. Identification of cross-reactive human single-chain variable fragments against phospholipases A2 from Lachesis muta and Bothrops spp venoms. Toxicon. 2020; 184 ():116-121.

Chicago/Turabian Style

Lucas B. Campos; Manuela B. Pucca; Luciano C. Silva; Gabriela Pessenda; Bruno A. Filardi; Felipe A. Cerni; Isadora S. Oliveira; Andreas H. Laustsen; Eliane C. Arantes; José E. Barbosa. 2020. "Identification of cross-reactive human single-chain variable fragments against phospholipases A2 from Lachesis muta and Bothrops spp venoms." Toxicon 184, no. : 116-121.

Immunology
Published: 22 May 2020 in Frontiers in Immunology
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Editorial: Novel Immunotherapies Against Envenomings by Snakes and Other Venomous Animals

ACS Style

Andreas Hougaard Laustsen; Stuart Ainsworth; Bruno Lomonte; R. Manjunatha Kini; Carlos Chávez-Olórtegui. Editorial: Novel Immunotherapies Against Envenomings by Snakes and Other Venomous Animals. Frontiers in Immunology 2020, 11, 1004 .

AMA Style

Andreas Hougaard Laustsen, Stuart Ainsworth, Bruno Lomonte, R. Manjunatha Kini, Carlos Chávez-Olórtegui. Editorial: Novel Immunotherapies Against Envenomings by Snakes and Other Venomous Animals. Frontiers in Immunology. 2020; 11 ():1004.

Chicago/Turabian Style

Andreas Hougaard Laustsen; Stuart Ainsworth; Bruno Lomonte; R. Manjunatha Kini; Carlos Chávez-Olórtegui. 2020. "Editorial: Novel Immunotherapies Against Envenomings by Snakes and Other Venomous Animals." Frontiers in Immunology 11, no. : 1004.

Review
Published: 12 May 2020 in Biomedicines
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Scorpion venom may cause severe medical complications and untimely death if injected into the human body. Neurotoxins are the main components of scorpion venom that are known to be responsible for the pathological manifestations of envenoming. Besides neurotoxins, a wide range of other bioactive molecules can be found in scorpion venoms. Advances in separation, characterization, and biotechnological approaches have enabled not only the development of more effective treatments against scorpion envenomings, but have also led to the discovery of several scorpion venom peptides with interesting therapeutic properties. Thus, scorpion venom may not only be a medical threat to human health, but could prove to be a valuable source of bioactive molecules that may serve as leads for the development of new therapies against current and emerging diseases. This review presents both the detrimental and beneficial properties of scorpion venom toxins and discusses the newest advances within the development of novel therapies against scorpion envenoming and the therapeutic perspectives for scorpion toxins in drug discovery.

ACS Style

Shirin Ahmadi; Julius M. Knerr; Lídia Argemi; Karla C. F. Bordon; Manuela B. Pucca; Felipe A. Cerni; Eliane C. Arantes; Figen Çalışkan; Andreas H. Laustsen. Scorpion Venom: Detriments and Benefits. Biomedicines 2020, 8, 118 .

AMA Style

Shirin Ahmadi, Julius M. Knerr, Lídia Argemi, Karla C. F. Bordon, Manuela B. Pucca, Felipe A. Cerni, Eliane C. Arantes, Figen Çalışkan, Andreas H. Laustsen. Scorpion Venom: Detriments and Benefits. Biomedicines. 2020; 8 (5):118.

Chicago/Turabian Style

Shirin Ahmadi; Julius M. Knerr; Lídia Argemi; Karla C. F. Bordon; Manuela B. Pucca; Felipe A. Cerni; Eliane C. Arantes; Figen Çalışkan; Andreas H. Laustsen. 2020. "Scorpion Venom: Detriments and Benefits." Biomedicines 8, no. 5: 118.

Original research article
Published: 07 May 2020 in Frontiers in Pharmacology
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Toxin synergism is a complex biochemical phenomenon, where different animal venom proteins interact either directly or indirectly to potentiate toxicity to a level that is above the sum of the toxicities of the individual toxins. This provides the animals possessing venoms with synergistically enhanced toxicity with a metabolic advantage, since less venom is needed to inflict potent toxic effects in prey and predators. Among the toxins that are known for interacting synergistically are cytotoxins from snake venoms, phospholipases A2 from snake and bee venoms, and melittin from bee venom. These toxins may derive a synergistically enhanced toxicity via formation of toxin complexes by hetero-oligomerization. Using a human keratinocyte assay mimicking human epidermis in vitro, we demonstrate and quantify the level of synergistically enhanced toxicity for 12 cytotoxin/melittin-PLA2 combinations using toxins from elapids, vipers, and bees. Moreover, by utilizing an interaction-based assay and by including a wealth of information obtained via a thorough literature review, we speculate and propose a mechanistic model for how toxin synergism in relation to cytotoxicity may be mediated by cytotoxin/melittin and PLA2 complex formation.

ACS Style

Manuela B. Pucca; Shirin Ahmadi; Felipe A. Cerni; Line Ledsgaard; Christoffer V. Sørensen; Farrell McGeoghan; Trenton Stewart; Erwin Schoof; Bruno Lomonte; Ulrich Auf Dem Keller; Eliane C. Arantes; Figen Çalışkan; Andreas H. Laustsen. Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A2 and Cytotoxins. Frontiers in Pharmacology 2020, 11, 1 .

AMA Style

Manuela B. Pucca, Shirin Ahmadi, Felipe A. Cerni, Line Ledsgaard, Christoffer V. Sørensen, Farrell McGeoghan, Trenton Stewart, Erwin Schoof, Bruno Lomonte, Ulrich Auf Dem Keller, Eliane C. Arantes, Figen Çalışkan, Andreas H. Laustsen. Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A2 and Cytotoxins. Frontiers in Pharmacology. 2020; 11 ():1.

Chicago/Turabian Style

Manuela B. Pucca; Shirin Ahmadi; Felipe A. Cerni; Line Ledsgaard; Christoffer V. Sørensen; Farrell McGeoghan; Trenton Stewart; Erwin Schoof; Bruno Lomonte; Ulrich Auf Dem Keller; Eliane C. Arantes; Figen Çalışkan; Andreas H. Laustsen. 2020. "Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A2 and Cytotoxins." Frontiers in Pharmacology 11, no. : 1.

Communication
Published: 09 April 2020 in Toxins
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Antibiotics are often administered with antivenom following snakebite envenomings in order to avoid secondary bacterial infections. However, to this date, no studies have evaluated whether antibiotics may have undesirable potentiating effects on snake venom. Herein, we demonstrate that four commonly used antibiotics affect the enzymatic activities of proteolytic snake venom toxins in two different in vitro assays. Similar findings in vivo could have clinical implications for snakebite management and require further examination.

ACS Style

Christoffer V. Sørensen; Cecilie Knudsen; Ulrich Auf Dem Auf Dem Keller; Konstantinos Kalogeropoulos; Cristina Gutiérrez-Jiménez; Manuela B. Pucca; Eliane C. Arantes; Karla C. F. Bordon; Andreas H. Laustsen. Do Antibiotics Potentiate Proteases in Hemotoxic Snake Venoms? Toxins 2020, 12, 240 .

AMA Style

Christoffer V. Sørensen, Cecilie Knudsen, Ulrich Auf Dem Auf Dem Keller, Konstantinos Kalogeropoulos, Cristina Gutiérrez-Jiménez, Manuela B. Pucca, Eliane C. Arantes, Karla C. F. Bordon, Andreas H. Laustsen. Do Antibiotics Potentiate Proteases in Hemotoxic Snake Venoms? Toxins. 2020; 12 (4):240.

Chicago/Turabian Style

Christoffer V. Sørensen; Cecilie Knudsen; Ulrich Auf Dem Auf Dem Keller; Konstantinos Kalogeropoulos; Cristina Gutiérrez-Jiménez; Manuela B. Pucca; Eliane C. Arantes; Karla C. F. Bordon; Andreas H. Laustsen. 2020. "Do Antibiotics Potentiate Proteases in Hemotoxic Snake Venoms?" Toxins 12, no. 4: 240.

Conference abstract
Published: 01 April 2020 in Toxicon
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ACS Style

Line Ledsgaard; Shirin Ahmadi; Manuela B. Pucca; Felipe A. Cerni; Jonas A. Jürgensen; Cecilie Knudsen; Urska Pus; Christoffer V. Sørensen; Sofie Føns; Rahel Janke; Julius Maximilian Knerr; Andreas Bertelsen; Rasmus I. Dehli; Andrea Martos Esteban; Aneesh Karatt-Vellatt; John McCafferty; Bruno Lomonte; Eliane Candiani Arantes; Andreas Hougaard Laustsen. Discovery of cross-reactive and recyclable human monoclonal antibodies for new recombinant antivenoms. Toxicon 2020, 177, S38 .

AMA Style

Line Ledsgaard, Shirin Ahmadi, Manuela B. Pucca, Felipe A. Cerni, Jonas A. Jürgensen, Cecilie Knudsen, Urska Pus, Christoffer V. Sørensen, Sofie Føns, Rahel Janke, Julius Maximilian Knerr, Andreas Bertelsen, Rasmus I. Dehli, Andrea Martos Esteban, Aneesh Karatt-Vellatt, John McCafferty, Bruno Lomonte, Eliane Candiani Arantes, Andreas Hougaard Laustsen. Discovery of cross-reactive and recyclable human monoclonal antibodies for new recombinant antivenoms. Toxicon. 2020; 177 ():S38.

Chicago/Turabian Style

Line Ledsgaard; Shirin Ahmadi; Manuela B. Pucca; Felipe A. Cerni; Jonas A. Jürgensen; Cecilie Knudsen; Urska Pus; Christoffer V. Sørensen; Sofie Føns; Rahel Janke; Julius Maximilian Knerr; Andreas Bertelsen; Rasmus I. Dehli; Andrea Martos Esteban; Aneesh Karatt-Vellatt; John McCafferty; Bruno Lomonte; Eliane Candiani Arantes; Andreas Hougaard Laustsen. 2020. "Discovery of cross-reactive and recyclable human monoclonal antibodies for new recombinant antivenoms." Toxicon 177, no. : S38.

Conference abstract
Published: 01 April 2020 in Toxicon
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Cecilie Knudsen; Søren Helweg Dam; Rasmus Ulslev Wegener Friis; Aleksander Moldt Haack; Jan Kuhlmann Andersen; Andreas Hougaard Laustsen. Discovery and evaluation of monoclonal antibodies for stratification of venoms from brazilian Bothrops, Crotalus, and Lachesis species. Toxicon 2020, 177, S38 .

AMA Style

Cecilie Knudsen, Søren Helweg Dam, Rasmus Ulslev Wegener Friis, Aleksander Moldt Haack, Jan Kuhlmann Andersen, Andreas Hougaard Laustsen. Discovery and evaluation of monoclonal antibodies for stratification of venoms from brazilian Bothrops, Crotalus, and Lachesis species. Toxicon. 2020; 177 ():S38.

Chicago/Turabian Style

Cecilie Knudsen; Søren Helweg Dam; Rasmus Ulslev Wegener Friis; Aleksander Moldt Haack; Jan Kuhlmann Andersen; Andreas Hougaard Laustsen. 2020. "Discovery and evaluation of monoclonal antibodies for stratification of venoms from brazilian Bothrops, Crotalus, and Lachesis species." Toxicon 177, no. : S38.

Conference abstract
Published: 01 April 2020 in Toxicon
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Jonas Arnold Jürgensen; Rahel Janke; Rasmus Ibsen Dehli; Andrea Martos-Esteban; Andreas Hougaard Laustsen. Harnessing monoclonal antibodies for development of a specific treatment against Naja nigricollis envenoming. Toxicon 2020, 177, S37 .

AMA Style

Jonas Arnold Jürgensen, Rahel Janke, Rasmus Ibsen Dehli, Andrea Martos-Esteban, Andreas Hougaard Laustsen. Harnessing monoclonal antibodies for development of a specific treatment against Naja nigricollis envenoming. Toxicon. 2020; 177 ():S37.

Chicago/Turabian Style

Jonas Arnold Jürgensen; Rahel Janke; Rasmus Ibsen Dehli; Andrea Martos-Esteban; Andreas Hougaard Laustsen. 2020. "Harnessing monoclonal antibodies for development of a specific treatment against Naja nigricollis envenoming." Toxicon 177, no. : S37.

Case report
Published: 01 January 2020 in Journal of Venomous Animals and Toxins including Tropical Diseases
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Snakebite envenoming can be a life-threatening condition, for which emergency care is essential. The Bothrops (lancehead) genus is responsible for most snakebite-related deaths and permanent loss of function in human victims in Latin America. Bothrops spp. venom is a complex mixture of different proteins that are known to cause local necrosis, coagulopathy, and acute kidney injury. However, the long-term effects of these viper envenomings have remained largely understudied. Here, we present a case report of a 46-years old female patient from Las Claritas, Venezuela, who was envenomed by a snake from the Bothrops genus. The patient was followed for a 10-year period, during which she presented oliguric renal failure, culminating in kidney failure 60 months after the envenoming. In Latin America, especially in Brazil, where there is a high prevalence of Bothrops envenoming, it may be relevant to establish long-term outpatient programs. This would reduce late adverse events, such as chronic kidney disease, and optimize public financial resources by avoiding hemodialysis and consequently kidney transplantation.

ACS Style

Manuela B. Pucca; Michelle V. S. Franco; Jilvando M. Medeiros; Isadora S. Oliveira; Shirin Ahmadi; Felipe A. Cerni; Umberto Zottich; Bruna K. Bassoli; Wuelton M. Monteiro; Andreas H. Laustsen. Chronic kidney failure following lancehead bite envenoming: a clinical report from the Amazon region. Journal of Venomous Animals and Toxins including Tropical Diseases 2020, 26, 1 .

AMA Style

Manuela B. Pucca, Michelle V. S. Franco, Jilvando M. Medeiros, Isadora S. Oliveira, Shirin Ahmadi, Felipe A. Cerni, Umberto Zottich, Bruna K. Bassoli, Wuelton M. Monteiro, Andreas H. Laustsen. Chronic kidney failure following lancehead bite envenoming: a clinical report from the Amazon region. Journal of Venomous Animals and Toxins including Tropical Diseases. 2020; 26 ():1.

Chicago/Turabian Style

Manuela B. Pucca; Michelle V. S. Franco; Jilvando M. Medeiros; Isadora S. Oliveira; Shirin Ahmadi; Felipe A. Cerni; Umberto Zottich; Bruna K. Bassoli; Wuelton M. Monteiro; Andreas H. Laustsen. 2020. "Chronic kidney failure following lancehead bite envenoming: a clinical report from the Amazon region." Journal of Venomous Animals and Toxins including Tropical Diseases 26, no. : 1.

Review article
Published: 06 September 2019 in Frontiers in Immunology
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Honey bees can be found all around the world and fulfill key pollination roles within their natural ecosystems, as well as in agriculture. Most species are typically docile, and most interactions between humans and bees are unproblematic, despite their ability to inject a complex venom into their victims as a defensive mechanism. Nevertheless, incidences of bee stings have been on the rise since the accidental release of Africanized bees to Brazil in 1956 and their subsequent spread across the Americas. These bee hybrids are more aggressive and are prone to attack, presenting a significant healthcare burden to the countries they have colonized. To date, treatment of such stings typically focuses on controlling potential allergic reactions, as no specific antivenoms against bee venom currently exist. Researchers have investigated the possibility of developing bee antivenoms, but this has been complicated by the very low immunogenicity of the key bee toxins, which fail to induce a strong antibody response in the immunized animals. However, with current cutting-edge technologies, such as phage display, alongside the rise of monoclonal antibody therapeutics, the development of a recombinant bee antivenom is achievable, and promising results towards this goal have been reported in recent years. Here, current knowledge on the venom biology of Africanized bees and current treatment options against bee envenoming are reviewed. Additionally, recent developments within next-generation bee antivenoms are presented and discussed.

ACS Style

Manuela B. Pucca; Felipe A. Cerni; Isadora S. Oliveira; Timothy P. Jenkins; Lídia Argemí; Christoffer V. Sørensen; Shirin Ahmadi; José E. Barbosa; Andreas Hougaard Laustsen. Bee Updated: Current Knowledge on Bee Venom and Bee Envenoming Therapy. Frontiers in Immunology 2019, 10, 2090 .

AMA Style

Manuela B. Pucca, Felipe A. Cerni, Isadora S. Oliveira, Timothy P. Jenkins, Lídia Argemí, Christoffer V. Sørensen, Shirin Ahmadi, José E. Barbosa, Andreas Hougaard Laustsen. Bee Updated: Current Knowledge on Bee Venom and Bee Envenoming Therapy. Frontiers in Immunology. 2019; 10 ():2090.

Chicago/Turabian Style

Manuela B. Pucca; Felipe A. Cerni; Isadora S. Oliveira; Timothy P. Jenkins; Lídia Argemí; Christoffer V. Sørensen; Shirin Ahmadi; José E. Barbosa; Andreas Hougaard Laustsen. 2019. "Bee Updated: Current Knowledge on Bee Venom and Bee Envenoming Therapy." Frontiers in Immunology 10, no. : 2090.

Review
Published: 01 September 2019 in Toxicon
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Snakebite envenoming is a devastating Neglected Tropical Disease, the treatment of which has seen relatively little innovation since the invention of antivenom serotherapy in 1894. Current antivenoms have been and continue to be invaluable in saving thousands of lives. However, these medicines are associated with a number of drawbacks pertaining to availability, safety, and efficacy. Fortunately, with the advent of novel methodologies, such as antibody discovery technologies, high-throughput drug discovery approaches, and improved methods for protein engineering, we are starting to see scientific advances in the field. This review presents relevant engineering and design considerations for exploiting these methodologies to develop next-generation antivenoms with improved safety, efficacy, and affordability. The pros and cons of different treatment modalities are discussed with regards to immunogenicity, the suitability of preclinical efficacy assays, availability of discovery methods, economic viability of production schemes, and possible regulatory approval paths.

ACS Style

Cecilie Knudsen; Line Ledsgaard; Rasmus Ibsen Dehli; Shirin Ahmadi; Christoffer Vinther Sørensen; Andreas Hougaard Laustsen. Engineering and design considerations for next-generation snakebite antivenoms. Toxicon 2019, 167, 67 -75.

AMA Style

Cecilie Knudsen, Line Ledsgaard, Rasmus Ibsen Dehli, Shirin Ahmadi, Christoffer Vinther Sørensen, Andreas Hougaard Laustsen. Engineering and design considerations for next-generation snakebite antivenoms. Toxicon. 2019; 167 ():67-75.

Chicago/Turabian Style

Cecilie Knudsen; Line Ledsgaard; Rasmus Ibsen Dehli; Shirin Ahmadi; Christoffer Vinther Sørensen; Andreas Hougaard Laustsen. 2019. "Engineering and design considerations for next-generation snakebite antivenoms." Toxicon 167, no. : 67-75.