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PSPT consortium

Description

On July 5th and 6th a hybrid meeting was held to present the results of the international assessment of the Pertussis Serological Potency Assay.

International assessment of the PSPT in mice to replace the intracerebral-challenge Mouse Protection Test (MPT) for whole-cell Pertussis (wP)

Whole-cell Pertussis (wP) containing vaccines are widely used for routine vaccination of children in several parts of the world as part of various combinations of vaccines in childhood immunization programs.

The standardization and control of wP vaccines was addressed by Kendrick in the 1930s, who developed a mouse protection assay involving intracerebral challenge with a lethal dose of the Bordetella pertussis to assess vaccine potency based on immunized animal survival in the period of two weeks after challenge. This Mouse Protection Test (MPT) or Kendrick Test shows high variability, requiring use of extensive numbers of animals which experience severe pain and distress. This project aims to support in-house assessment of a serological assay (Pertussis Serological Potency Test – PSPT) to enable the transition from intracerebral challenge to immunization, to assess the potency of wP containing vaccines with an ELISA, to reduce variability of the test, the numbers of animals and the level of distress. The PSPT was evaluated in mice and guinea pigs favourably in published studies allowing for discrimination of vaccine batch potency and use of the test for demonstration of consistency in production. Hence, the assessment of PSPT is now a critical step.
An ad hoc Steering Group will guide the Consortium on all the scientific and technical aspects of the project.

The report of the DCVMN PSPT Project has been published in the WHO Drug Information Publication. It can be downloaded from this link: https://www.who.int/publications/i/item/9789240107038

You can also download the publication Here

Project’s Participants

Project’s ParticipantType of LaboratoryLocationwP-containing Products ReleasedBatch Release Methods
National Control Laboratory IndonesiaDTP
DTP-Hep B-Hib		Kendrick Test
or Mouse Protection Test
Vaccine ManufacturerIndiaDTP
DTPHib
DTPHepBHib		Kendrick Test
or Mouse Protection Test
Vaccine ManufacturerIndonesiaDTP
DTPHepBHib
Monovalent whole cell pertussis bulk 		Kendrick Test
or Mouse Protection Test
Vaccine ManufacturerIndiaDTPHepBHib
DTwP
DTwP Hep B
DTwPHib (under development)
DTwPHep BHib IPV (under development)		Kendrick Test
or Mouse Protection Test
Vaccine ManufacturerIndiaDTPHib
DTPHepBHib
DTPHepBHibIPV 		Kendrick Test
or Mouse Protection Test
Vaccine ManufacturerBulgariaDTPKendrick Test
or Mouse Protection Test
National Control LaboratoryIndiaDTP
DTPHepB
DTPHib
DTPHepBHib
DTPHepBHibIPV 		Kendrick Test
or Mouse Protection Test
National Control LaboratoryThailandDTP
DTPHB
DTPHBHib
DTPIPVHB		Kendrick Test
or Mouse Protection Test
Vaccine ManufacturerIndiaDTPHepBHibKendrick Test
or Mouse Protection Test
Vaccine ManufacturerIndiaDTPHepBHibKendrick Test
or Mouse Protection Test

Steering Group Section

PSPT Consortium Steering Group

Documents and Meeting Minutes
DCVMN PSPT 15th Technical Workshop June 23rd 2022
DCVMN PSPT 14th Technical Workshop March 31st 2022
DCVMN PSPT 13th Technical Workshop Dec 2nd 2021
DCVMN PSPT 12th Technical Workshop Oct 28 2021
DCVMN PSPT 11th Technical Workshop Sep 30 2021
DCVMN PSPT 10th Technical Workshop Aug 26 2021
DCVMN PSPT 9th Technical Workshop Jul 29 2021
DCVMN PSPT 8th Technical Workshop Jun 24 2021
DCVMN PSPT 7th Technical Workshop May 27 2021
DCVMN PSPT 6th technical Workshop April 29 2021
DCVMN PSPT 5th Technical Workshop March 25 2021
DCVMN PSPT 4th Technical Workshop Feb 25 2021 minutes
DCVMN PSPT 3rd Technical Workshop Jan 29 2021 minutes
DCVMN PSPT 2nd Technical Workshop Dec 10 2020 minutes
DCVMN PSPT 1st Technical workshop 22nd October 2020 minutes
Meeting minutes DCVMN PSPT kick off meeting Sep 29 2020
PSPT Steering Group Meeting Minutes Sept 2020

Document NameTypeDescriptionLink
DCVMN Proposal to NIIMBL – Project Call 3.1GWordDetailed overview of project aims goal and projected timelin
PSPT Project Management and Steering GroupPPT
PSPT Participating LaboratoriesPPTManufacturers and Laboratories who have agreed to participate in the PSPT
PPSPT In-House validationPPT
Alternatives to HIST for acellular pertussis vaccines: progress and challenges in replacementPDFDiscussion from 2014 workshop focused on the progress and challenges associated with the development, validation, and implementation of in vitro assays as replacements for the histamine sensitisation test (HIST) for acellular pertussis vaccines.
Development and implementation of standardized method for detecting immunogenicity of acellular pertussis vaccines in KoreaPDFDevelopment and evaluation of an ELISA based immunogenicity test of 3-component aP vaccines produced in Korea using WHO sera as reference.
Target alternative vaccine safety testing strategies for pertussis toxinPDFOverview of alternative strategies to the histamine sensitizations assay, primarily the Japanese temperature drop assay and in- vitro assays (enzymatic activity assay and a binding assay).
Assessment of safety and efficacy against Bordetella pertussis of a new tetanus reduced dose diphtheria-acellular pertussis vaccine in a murine modelPDFA Korean lead study to evaluate the immunogenicity, safety, and protection efficacy against Bordetella pertussis of the new Tdap vaccine in a murine model.
The History of Pertussis (Whooping Cough); 1906–2015: Facts, Myths, and MisconceptionsPDFOverview of history and pathology of Pertussis
PERISCOPE: Road towards effective control of pertussisPDFAddresses several key obstacles on the path to developing a durable solution for global control of pertussis by the Pertussis Correlates Of Protection Europe (PERISCOPE) Consortium was established in March, 2016.
Humane endpoints in vaccine potency testingPDFDevelopment of 3R potency testing that include a nonclinical endpoint, ultimately resulting in reduction of animal numbers and a significant decrease in severity level (sera based potency testing of DtT)and the implementation of humane endpoints to limit the level and duration of pain and distress.
Towards replacement of the acellular pertussis vaccine safety test: Comparison of in vitro cytotoxic activity and in vivo activity in micePDFStudy compares the sensitivity of the in vivo HIST with an in vitro Chinese Hamster Ovary (CHO) cell-based assay. Using vaccine samples that had been spiked with PTx, found that both assays were capable of detecting as little as 4–10 ng of active pertussis toxin per dose of vaccine; thus, the sensitivities of the two assays are comparables.
Safety testing of acellular pertussis vaccines: Use of animals and 3Rs alternativesPDFStudy evaluates estimate the number of mice used worldwide for HIST by major aP manufacturers and why the efforts needed for validation and implementation of these interim alternatives may not be worthwhile, when there are several in vitro alternatives in various stages of development.
In search of acceptable alternatives to the murine histamine sensitisation test (HIST): what is possible and practical?PDFValidation of 2 modified CHO cell protocols (the Direct and the Indirect Methods) for further consideration as alternatives to HIST.
Collaborative Study: Evaluation of Proposed Second International Standard for Pertussis ToxinPDFEvaluation of CHO and biochemical pertussis potency assays as alternative to HIST Test within parameters laid out by the WHO.
Whole-cell pertussis vaccine potency assays: the Kendrick test and alternative assaysPDFA review of the Kendrick test in terms of international requirements for vaccine potency and critical technical points to be considered for a successful test including test validity, in-house references and statistical analysis.
Evaluation of Two Serological Methods for Potency Testing of Whole Cell Pertussis VaccinesPDFStudy evaluates features of the serological response to wP vaccination: 1) the overall antibody response as measured by a “whole cell”” ELISA (PSPT-wC-ELISA) which uses the B. pertussis 18323 challenge strain prescribed for the MPT to coat the assay plates and 2) the functional neutralising antibodies to pertussis toxin (PT, one of the main virulence factors of B. pertussis), as measured by the Chinese Hamster Ovary (CHO) cell assay.
Consortium Agreements
CA – Biofarma
CA – Biological E
CA – BulBio
CA – CDL_Kasauli
CA – Central Laboratory Thailand
CA – National Institute of Public Health
CA – Panacea
CA – Pasteur Institute of India
CA – Serum Institute DCVMN

Project Final Meeting

pspt_meeting_banner.png
Presentations
PSPT Project Scope and Participants
PSPT Project Outcomes
BioLyo Coating Antigen Production
Intravacc Coating antigen characterization
PSPT Study design, Protocols and setting
PSPT Statistical Analysis
PSPT Challenges and proposed solutions
Mantis_Antibody-based methodology to assess the stability of wP vaccines
Procedures and Working Documents
PSPT-ELISA Work Protocol (word)
PSPT In Vivo Work Protocol (word)
Spreadsheet – PSPT ELISA 2.0 Fold Dilution (excel)
Spreadsheet – PSPT ELISA 2.5 Fold Dilution (excel)
Spreadsheet – General Purpose PC Screening (excel)
Spreadsheet – Titration of Biotin IgG and streptavidin (excel)