Variability of in vivo potency tests of Diphtheria, Tetanus and acellular Pertussis (DTaP) vaccines

Stalpers, Coen A.L.; Retmana, Irene A.; Pennings, Jeroen L. A.; Vandebriel, Rob J.; Hendriksen, Coenraad; Akkermans, Arnoud; Hoefnagel, Marcel H. N.

doi:10.1016/j.vaccine.2021.03.078

Cited by 20 publications

(14 citation statements)

References 20 publications

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“…Although it is not possible to directly correlate the formation kinetics of a single peptide or a group of peptides to in vivo efficacy or toxicity, these kinetics could be used for the development of an assay that measures consistency between batches without the use of animal studies. The current animal tests have notoriously high variability and insensitivity which makes direct comparison between new assays and animal tests difficult . Historic data has shown that toxoid vaccines are very stable when stored correctly, but exposure to elevated temperaturessimilar to those used in the current studycan decrease the potency .…”

Section: Resultsmentioning

confidence: 99%

“…The current animal tests have notoriously high variability and insensitivity which makes direct comparison between new assays and animal tests difficult. 29 Historic data has shown that toxoid vaccines are very stable when stored correctly, but exposure to elevated temperaturessimilar to those used in the current study can decrease the potency. 30 Depending on how sensitive the chosen peptides are, the differences in kinetics can distinguish even changes in the toxoid induced by exposure to 37 °C compared to the controls.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Common Reference-Based Tandem Mass Tag Multiplexing for the Relative Quantification of Peptides: Design and Application to Degradome Analysis of Diphtheria Toxoid

Michiels

Veen

Meiring

et al. 2021

J. Am. Soc. Mass Spectrom.

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Currently, animal tests are being used to confirm the potency and lack of toxicity of toxoid vaccines. In a consistency approach, animal tests could be replaced if production consistency (compared to known good products) can be proven in a panel of in vitro assays. By mimicking the in vivo antigen processing in a simplified in vitro approach, it may be possible to distinguish aberrant products from good products. To demonstrate this, heat-exposed diphtheria toxoid was subjected to partial digestion by cathepsin S (an endoprotease involved in antigen processing), and the peptide formation/degradation kinetics were mapped for various heated toxoids. To overcome the limitations associated with the very large number of samples, we used common reference-based tandem mass tag (TMT) labeling. Instead of using one label per condition with direct comparison between the set of labels, we compared multiple labeled samples to a common reference (a pooled sample containing an aliquot of each condition). In this method, the number of samples is not limited by the number of unique TMT labels. This TMT multiplexing strategy allows for a 15-fold reduction of analysis time while retaining the reliability advantage of TMT labeling over label-free quantification. The formation of the most important peptides could be followed over time and compared among several conditions. The changes in enzymatic degradation kinetics of diphtheria toxoid revealed several suitable candidate peptides for use in a quality control assay that can distinguish structurally aberrant diphtheria toxoid from compliant toxoids.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Common Reference-Based Tandem Mass Tag Multiplexing for the Relative Quantification of Peptides: Design and Application to Degradome Analysis of Diphtheria Toxoid

Michiels

Veen

Meiring

et al. 2021

J. Am. Soc. Mass Spectrom.

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“…This has led to a paradox in which improved quality of vaccines makes it more difficult to validate new in vitro test methods. Another problem is the inherent variability of current in vivo release tests that are used as reference tests, which may limit the ability to which they can discriminate between batches of different quality [7][8][9][10][11][12]125]. In other words, in vivo tests may show variation to an extent that some batches fail the test, while they are in fact compliant, i.e.…”

Section: Altered Batches To Validate In Vitro Test Methodsmentioning

confidence: 99%

“…In other words, in vivo tests may show variation to an extent that some batches fail the test, while they are in fact compliant, i.e. their capacity to induce protective immunity in the target species is sufficient [125]. Such batches can be expected to pass appropriate in vitro tests.…”

Section: Altered Batches To Validate In Vitro Test Methodsmentioning

confidence: 99%

Overcoming scientific barriers in the transition fromin vivoto non-animal batch testing of human and veterinary vaccines

Biggelaar

Hoefnagel

Vandebriel

et al. 2021

Expert Review of Vaccines

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Introduction: Before release, vaccine batches are assessed for quality to evaluate whether they meet the product specifications. Vaccine batch tests, in particular of inactivated and toxoid vaccines, still largely rely on in vivo methods. Improved vaccine production processes, ethical concerns, and suboptimal performance of some in vivo tests have led to the development of in vitro alternatives.Areas covered: This review describes the scientific constraints that need to be overcome for replacement of in vivo batch tests, as well as potential solutions. Topics include the critical quality attributes of vaccines that require testing, the use of cell-based assays to mimic aspects of in vivo vaccine-induced immune responses, how difficulties with testing adjuvanted vaccines in vitro can be overcome, the use of altered batches to validate new in vitro test methods, and how cooperation between different stakeholders is key to moving the transition forward. Expert opinion: For safety testing, many in vitro alternatives are already available or at an advanced level of development. For potency testing, in vitro alternatives largely comprise immunochemical methods that assess several, but not all critical vaccine properties. One-to-one replacement by in vitro alternatives is not always possible and a combination of methods may be required.

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“…Soluble N-ethylmale-imide-sensitive factor-attachment protein receptors (SNAREs) play an indispensable role in membrane attachment events in eukaryotic cells ( Yoo et al, 2021 ). Neurotransmitter released is blocked by clostridia neurotoxin in vivo by selective proteolysis of synaptic SNAREs ( Nesil and Erbas, 2021 , Stalpers et al, 2021 ). Tetanus toxoid is a Food and Drug Administration (FDA), USA approved vaccine that protects the body from the effects of clostridium neurotoxins, which block the inhibitory neurotransmitter and lead to spasms ( O’Neil et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis of antigenic strength and in vivo serum antibodies concentration of tetanus toxoid vaccine adsorbed in Pakistan

Zahid

Farooqi

Ahsan

et al. 2022

Saudi Journal of Biological Sciences

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Variability of in vivo potency tests of Diphtheria, Tetanus and acellular Pertussis (DTaP) vaccines

Cited by 20 publications

References 20 publications

Common Reference-Based Tandem Mass Tag Multiplexing for the Relative Quantification of Peptides: Design and Application to Degradome Analysis of Diphtheria Toxoid

Common Reference-Based Tandem Mass Tag Multiplexing for the Relative Quantification of Peptides: Design and Application to Degradome Analysis of Diphtheria Toxoid

Overcoming scientific barriers in the transition fromin vivoto non-animal batch testing of human and veterinary vaccines

Comparative analysis of antigenic strength and in vivo serum antibodies concentration of tetanus toxoid vaccine adsorbed in Pakistan

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