Evaluation of the monocyte activation test for the safety testing of meningococcal B vaccine Bexsero: A collaborative study

Studholme, Lucy; Sutherland, Janet; Desai, Trusha; Hockley, Jason; Care, Rory; Nordgren, Ida Karin; Vipond, Caroline

doi:10.1016/j.vaccine.2018.05.073

Cited by 12 publications

(10 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For vaccine batch release, it is important to confirm that the pyrogenic response is maintained at safe levels. Historic use of the RPT for batch release of Bexsero, an OMV-based meningococcal B vaccine, proved problematic due to inconsistencies and false-positive test results contributed by extensive dilution of the vaccine product due to its intrinsic pyrogenic properties [ 17 , 32 ]. In addition, BET is not a suitable replacement for OMV-based vaccines due to the complexity of pathogen-associated molecular patterns (PAMPs) and the inability of this test to detect pyrogens of non-endotoxin origin.…”

Section: Discussionmentioning

confidence: 99%

“…However, vaccines are most commonly delivered via other administration routes, such as intramuscularly in the case of Shigella GMMA. Implementation of the RPT for the safety testing of the meningococcal OMV-based vaccine Bexsero gave a measure of batch consistency that is prone to false-positive results [ 17 , 18 ]. An adaptation to deliver a full human dose of vaccine intramuscularly to the rabbit (mRPT) was developed for testing 1790GAHB.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Development of a Monocyte Activation Test as an Alternative to the Rabbit Pyrogen Test for Mono- and Multi-Component Shigella GMMA-Based Vaccines

et al. 2021

Self Cite

View full text Add to dashboard Cite

Generalised modules for membrane antigens (GMMA)-based vaccines comprise the outer membrane from genetically modified Gram-negative bacteria containing membrane proteins, phospholipids and lipopolysaccharides. Some lipoproteins and lipopolysaccharides are pyrogens; thus, GMMA-based vaccines are intrinsically pyrogenic. It is important to control the pyrogenic content of biological medicines, including vaccines, to prevent adverse reactions such as febrile responses. The rabbit pyrogen test (RPT) and bacterial endotoxin test (BET) are the most commonly employed safety assays used to detect pyrogens. However, both tests are tailored for detecting pyrogenic contaminants and have considerable limitations when measuring the pyrogen content of inherently pyrogenic products. We report the adaptation of the monocyte activation test (MAT) as an alternative to the RPT for monitoring the pyrogenicity of Shigella GMMA-based vaccines. The European Pharmacopoeia endorses three MAT methods (A–C). Of these, method C, the reference lot comparison test, was identified as the most suitable. This method was evaluated with different reference materials to ensure parallelism and consistency for a mono- and multi-component Shigella GMMA vaccine. We demonstrate the drug substance as a promising reference material for safety testing of the matched drug product. Our results support the implementation of MAT as an alternative to the RPT and use of the defined parameters can be extended to GMMA-based vaccines currently in development, aiding vaccine batch release.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of a Monocyte Activation Test as an Alternative to the Rabbit Pyrogen Test for Mono- and Multi-Component Shigella GMMA-Based Vaccines

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Nowadays, the blood clotting factor C (rFC) from the horseshoe crab is commercially available as a recombinant protein, but the rFC test has been implemented to a limited extent despite its proven efficacy and its adoption in the European Pharmacopoeia as alternative reagent in endotoxin tests (general text 2.6.14, 2.6.32 and 5.1.10) [17,42]. The Monocyte Activation Test (MAT) was developed to detect both endotoxin and nonendotoxin pyrogens [44][45][46]. In this test human whole blood or (cryopreserved) PBMCs are stimulated with the vaccine of interest after which the production of pro-inflammatory cytokines (TNF, IL-1β and IL-6) is assessed in ELISAs.…”

Section: Article Highlightsmentioning

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

View full text Add to dashboard Cite

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.

show abstract

“…Currently, MAT is employed by both OMCLs and manufacturers for the batch release of the Neisseria meningitidis group B vaccine (Bexsero®) [ 16 ] while, by OMCLs only for the Salmonella Typhi vaccine ( Typhim Vi® ). RPT is state of the art for multivalent DTwP-HepB vaccine, vaccines against human rabies, pneumococcal and meningococcal polysaccharide vaccine, and TBEV.…”

Section: Animal Use and 3rsmentioning

confidence: 99%

Animal testing for vaccines. Implementing replacement, reduction and refinement: challenges and priorities

Akkermans

Chapsal²,

Coccia

et al. 2020

Biologicals

View full text Add to dashboard Cite

Transition to in vitro alternative methods to in vivo in vaccine release testing and characterization, the implementation of the consistency approach, and a drive towards international harmonization of regulatory requirements are most pressing needs in the field of vaccines. It is critical for global vaccine community to work together to secure effective progress towards animal welfare and to ensure that vaccines of ever higher quality can reach the populations in need in the shortest possible timeframe. Advancements in the field, case studies, and experiences from Low and Middle Income Countries (LMIC) were the topics discussed by an international gathering of experts during a recent conference titled “ Animal Testing for Vaccines – Implementing Replacement, Reduction and Refinement: Challenges and Priorities ”. This conference was organized by the International Alliance for Biological Standardization (IABS), and held in Bangkok, Thailand on December 3 and 4 2019. Participants comprised stakeholders from many parts of the world, including vaccine developers, manufacturers and regulators from Asia, Europe, North America, Australia and New Zealand. In interactive workshops and vibrant panel discussions, the attendees worked together to identify the remaining barriers to validation, acceptance and implementation of alternative methods, and how harmonization could be promoted, especially for LMICs.

show abstract

Evaluation of the monocyte activation test for the safety testing of meningococcal B vaccine Bexsero: A collaborative study

Cited by 12 publications

References 29 publications

Development of a Monocyte Activation Test as an Alternative to the Rabbit Pyrogen Test for Mono- and Multi-Component Shigella GMMA-Based Vaccines

Development of a Monocyte Activation Test as an Alternative to the Rabbit Pyrogen Test for Mono- and Multi-Component Shigella GMMA-Based Vaccines

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

Animal testing for vaccines. Implementing replacement, reduction and refinement: challenges and priorities

Contact Info

Product

Resources

About