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PSPT Consortium

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.

On July 5th and 6th DCVMN will presents the results of the international assessment of the Pertussis Serological Potency Assay.
Join the online meeting starting from 12 PM CEST registering here:
Day 1: https://us06web.zoom.us/meeting/register/tZMkdO6qpzMtHtaNbzrVsny30YnLh1vPOYn0
Day 2: https://us06web.zoom.us/meeting/register/tZEpfumhpzIiH9DOIkjaVmcEEvKn1y8MYw1E

Download the agenda

Members

Member	Type of Laboratory	Location	wP-containing Products Released	Batch Release Methods
Bhadan Pom	National Control Laboratory	Indonesia	DTP DTP-Hep B-Hib	Kendrick Test or Mouse Protection Test
Bharat Biotech	Vaccine Manufacturer	India	DTP DTPHib DTPHepBHib	Kendrick Test or Mouse Protection Test
Biofarma	Vaccine Manufacturer	Indonesia	DTP DTPHepBHib Monovalent whole cell pertussis bulk	Kendrick Test or Mouse Protection Test
Biological E	Vaccine Manufacturer	India	DTPHepBHib DTwP DTwP Hep B DTwPHib (under development) DTwPHep BHib IPV (under development)	Kendrick Test or Mouse Protection Test
Panacea Biotec	Vaccine Manufacturer	India	DTPHib DTPHepBHib DTPHepBHibIPV	Kendrick Test or Mouse Protection Test
BulBio	Vaccine Manufacturer	Bulgaria	DTP	Kendrick Test or Mouse Protection Test
Central Drugs Laboratory, Kasauli, INDIA	National Control Laboratory	India	DTP DTPHepB DTPHib DTPHepBHib DTPHepBHibIPV	Kendrick Test or Mouse Protection Test
Institute of Biological Products	National Control Laboratory	Thailand	DTP DTPHB DTPHBHib DTPIPVHB	Kendrick Test or Mouse Protection Test
Intravacc	Research institute	The Netherland	NA	NA
National Institute of Public Health National Institute of Hygiene	Research institute National control laboratory	Poland	DTP	Kendrick Test or Mouse Protection Test
Serum Institute of India	Vaccine Manufacturer	India	DTwPHepBHib DTwP Hexavalent vaccine under development	Kendrick Test or Mouse Protection Test
Sanofi Healthcare India Pvt. Ltd	Vaccine Manufacturer	India	DTPHepBHib	Kendrick Test or Mouse Protection Test
Pasteur Institute of India	Vaccine Manufacturer Research institute	India	DTP	Kendrick Test or Mouse Protection Test

Steering Group

PSPT Consortium Steering Group

Documents and Meeting Minutes

Key publications related to the PSPT project

Document Name	Type	Description	Link
DCVMN Proposal to NIIMBL - Project Call 3.1G	Word	Detailed overview of project aims goal and projected timelin
PSPT Project Management and Steering Group	PPT
PSPT Participating Laboratories	PPT	Manufacturers and Laboratories who have agreed to participate in the PSPT
PPSPT In-House validation	PPT
Alternatives to HIST for acellular pertussis vaccines: progress and challenges in replacement	PDF	Discussion 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.	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980995/
Development and implementation of standardized method for detecting immunogenicity of acellular pertussis vaccines in Korea	PDF	Development and evaluation of an ELISA based immunogenicity test of 3-component aP vaccines produced in Korea using WHO sera as reference.	https://pubmed.ncbi.nlm.nih.gov/30775349/
Target alternative vaccine safety testing strategies for pertussis toxin	PDF	Overview 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).	https://www.sciencedirect.com/science/article/pii/S1877282X11000440
Assessment of safety and efficacy against Bordetella pertussis of a new tetanus reduced dose diphtheria-acellular pertussis vaccine in a murine model	PDF	A Korean lead study to evaluate the immunogenicity, safety, and protection efficacy against Bordetella pertussis of the new Tdap vaccine in a murine model.	https://pubmed.ncbi.nlm.nih.gov/28376777&
The History of Pertussis (Whooping Cough); 1906–2015: Facts, Myths, and Misconceptions	PDF	Overview of history and pathology of Pertussis	https://link.springer.com/article/10.1007/s40471-015-0041-9
PERISCOPE: Road towards effective control of pertussis	PDF	Addresses 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.	thelancet.com/journals/laninf/article/PIIS1473-3099(18)30646-7/fulltext
Humane endpoints in vaccine potency testing	PDF	Development 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.	https://www.sciencedirect.com/science/article/pii/S1877282X11000403
Towards replacement of the acellular pertussis vaccine safety test: Comparison of in vitro cytotoxic activity and in vivo activity in mice	PDF	Study 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.	https://pubmed.ncbi.nlm.nih.gov/29122386/
Safety testing of acellular pertussis vaccines: Use of animals and 3Rs alternatives	PDF	Study 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.	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703371/
In search of acceptable alternatives to the murine histamine sensitisation test (HIST): what is possible and practical?	PDF	Validation of 2 modified CHO cell protocols (the Direct and the Indirect Methods) for further consideration as alternatives to HIST.	https://pubmed.ncbi.nlm.nih.gov/28279256/
Collaborative Study: Evaluation of Proposed Second International Standard for Pertussis Toxin	PDF	Evaluation of CHO and biochemical pertussis potency assays as alternative to HIST Test within parameters laid out by the WHO.	https://apps.who.int/iris/handle/10665/260487
Whole-cell pertussis vaccine potency assays: the Kendrick test and alternative assays	PDF	A 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.	https://pubmed.ncbi.nlm.nih.gov/25182836/
Evaluation of Two Serological Methods for Potency Testing of Whole Cell Pertussis Vaccines	PDF	Study 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.	https://pubmed.ncbi.nlm.nih.gov/19220977/

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 - Serum Institute DCVMN
CA - Pasteur Institute of India