Engineering and design considerations for next-generation snakebite antivenoms

Cecilie Knudsen*, Line Ledsgaard, Rasmus Ibsen Dehli, Shirin Ahmadi, Christoffer Vinther Sørensen, Andreas Hougaard Laustsen

*Corresponding author for this work

Research output: Contribution to journalReviewResearchpeer-review

Abstract

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.

Original languageEnglish
JournalToxicon
Volume167
Pages (from-to)67-75
Number of pages9
ISSN0041-0101
DOIs
Publication statusPublished - 2019

Keywords

  • Antivenom development
  • Antivenom manufacture
  • Monoclonal antibodies
  • Next-generation antivenoms
  • Recombinant antivenoms
  • Small molecule toxin inhibitors
  • Snakebite envenoming
  • Toxin-neutralization

Cite this

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title = "Engineering and design considerations for next-generation snakebite antivenoms",
abstract = "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.",
keywords = "Antivenom development, Antivenom manufacture, Monoclonal antibodies, Next-generation antivenoms, Recombinant antivenoms, Small molecule toxin inhibitors, Snakebite envenoming, Toxin-neutralization",
author = "Cecilie Knudsen and Line Ledsgaard and Dehli, {Rasmus Ibsen} and Shirin Ahmadi and S{\o}rensen, {Christoffer Vinther} and Laustsen, {Andreas Hougaard}",
year = "2019",
doi = "10.1016/j.toxicon.2019.06.005",
language = "English",
volume = "167",
pages = "67--75",
journal = "Toxicon",
issn = "0041-0101",
publisher = "Pergamon Press",

}

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

In: Toxicon, Vol. 167, 2019, p. 67-75.

Research output: Contribution to journalReviewResearchpeer-review

TY - JOUR

T1 - Engineering and design considerations for next-generation snakebite antivenoms

AU - Knudsen, Cecilie

AU - Ledsgaard, Line

AU - Dehli, Rasmus Ibsen

AU - Ahmadi, Shirin

AU - Sørensen, Christoffer Vinther

AU - Laustsen, Andreas Hougaard

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Antivenom development

KW - Antivenom manufacture

KW - Monoclonal antibodies

KW - Next-generation antivenoms

KW - Recombinant antivenoms

KW - Small molecule toxin inhibitors

KW - Snakebite envenoming

KW - Toxin-neutralization

U2 - 10.1016/j.toxicon.2019.06.005

DO - 10.1016/j.toxicon.2019.06.005

M3 - Review

VL - 167

SP - 67

EP - 75

JO - Toxicon

JF - Toxicon

SN - 0041-0101

ER -