<div class="csl-bib-body">
<div class="csl-entry">Kurtović, T., Lang Balija, M., Brgles, M., Sviben, D., Tunjić, M., Cajner, H., Marchetti-Deschmann, M., Allmaier, G., & Halassy, B. (2019). Refinement strategy for antivenom preparation of high yield and quality. <i>PLoS Neglected Tropical Diseases</i>, <i>13</i>(6), Article e0007431. https://doi.org/10.1371/journal.pntd.0007431</div>
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dc.identifier.issn
1935-2735
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dc.identifier.uri
http://hdl.handle.net/20.500.12708/144113
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dc.description.abstract
Antivenoms from hyperimmune animal plasma are the only specific pharmaceuticals against snakebites. The improvement of downstream processing strategies is of great interest, not only in terms of purity profile, but also from yield-to-cost perspective and rational use of plasma of animal origin. We report on development of an efficient refinement strategy for F(ab')₂-based antivenom preparation. Process design was driven by the imperative to keep the active principle constantly in solution as a precautionary measure to preserve stability of its conformation (precipitation of active principle or its adsorption to chromatographic stationary phase has been completely avoided). IgG was extracted from hyperimmune horse plasma by 2% (V/V) caprylic acid, depleted from traces of precipitating agent and digested by pepsin. Balance between incomplete IgG fraction breakdown, F(ab')₂ over-digestion and loss of the active principle's protective efficacy was achieved by adjusting pepsin to substrate ratio at the value of 4:300 (w/w), setting pH to 3.2 and incubation period to 1.5 h. Final polishing was accomplished by a combination of diafiltration and flow-through chromatography. Developed manufacturing strategy gave 100% pure and aggregate-free F(ab')₂ preparation, as shown by size-exclusion HPLC and confirmed by MS/MS. The overall yield of 75% or higher compares favorably to others so far reported. This optimised procedure looks also promising for large-scale production of therapeutic antivenoms, since high yield of the active drug and fulfillment of the regulatory demand considering purity was achieved. The recovery of the active substance was precisely determined in each purification step enabling accurate estimation of the process cost-effectiveness.
en
dc.language.iso
en
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dc.publisher
PUBLIC LIBRARY SCIENCE
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dc.relation.ispartof
PLoS Neglected Tropical Diseases
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dc.subject
Public Health
en
dc.subject
Infectious Diseases
en
dc.subject
Environmental and Occupational Health
en
dc.title
Refinement strategy for antivenom preparation of high yield and quality
en
dc.type
Artikel
de
dc.type
Article
en
dc.contributor.affiliation
University of Zagreb, Croatia
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dc.contributor.affiliation
University of Zagreb, Croatia
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dc.contributor.affiliation
University of Zagreb, Croatia
-
dc.contributor.affiliation
University of Zagreb, Croatia
-
dc.contributor.affiliation
University of Zagreb
-
dc.contributor.affiliation
University of Zagreb, Croatia
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dc.contributor.affiliation
University of Zagreb, Croatia
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dc.type.category
Original Research Article
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tuw.container.volume
13
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tuw.container.issue
6
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tuw.journal.peerreviewed
true
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tuw.peerreviewed
true
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wb.publication.intCoWork
International Co-publication
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tuw.researchTopic.id
M6
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tuw.researchTopic.name
Biological and Bioactive Materials
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tuw.researchTopic.value
100
-
dcterms.isPartOf.title
PLoS Neglected Tropical Diseases
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tuw.publication.orgunit
E164-01-1 - Forschungsgruppe Massenspektrometrische Bio- und Polymeranalytik
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tuw.publisher.doi
10.1371/journal.pntd.0007431
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dc.identifier.articleid
e0007431
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dc.identifier.eissn
1935-2735
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dc.description.numberOfPages
23
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tuw.author.orcid
0000-0002-4816-7278
-
tuw.author.orcid
0000-0002-8060-7851
-
tuw.author.orcid
0000-0002-1438-9462
-
wb.sci
true
-
wb.sciencebranch
Chemie
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wb.sciencebranch
Medizintechnik
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wb.sciencebranch.oefos
1040
-
wb.sciencebranch.oefos
2060
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wb.facultyfocus
Bioscience Technology
de
wb.facultyfocus
Bioscience Technology
en
wb.facultyfocus.faculty
E150
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item.grantfulltext
restricted
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item.openairetype
research article
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item.fulltext
no Fulltext
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item.languageiso639-1
en
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item.openairecristype
http://purl.org/coar/resource_type/c_2df8fbb1
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item.cerifentitytype
Publications
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crisitem.author.dept
University of Zagreb
-
crisitem.author.dept
University of Zagreb
-
crisitem.author.dept
University of Zagreb
-
crisitem.author.dept
University of Zagreb
-
crisitem.author.dept
E164 - Institut für Chemische Technologien und Analytik
-
crisitem.author.dept
E164-01-1 - Forschungsgruppe Massenspektrometrische Bio- und Polymeranalytik
-
crisitem.author.orcid
0000-0002-8060-7851
-
crisitem.author.orcid
0000-0002-1438-9462
-
crisitem.author.parentorg
E150 - Fakultät für Technische Chemie
-
crisitem.author.parentorg
E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie