2006-03-14-世界卫生组织-Working_Group_on_standardization_control_of_acellular_pertussis_vaccines_16页_140kb

Summary of WHO Working Group on Standardization and Control of Acellular Pertussis Vaccines Report (2006)

This report summarizes the deliberations of a WHO expert working group held in St. Albans, UK, on 16–17 March 2006. The meeting focused on revising WHO guidelines for the production, control, and evaluation of acellular pertussis (aP) vaccines, building on previous discussions and data collection.

Key Objectives

• To review the scientific basis for updating WHO guidelines adopted in 1996.
• To address challenges in quality control (QC), including assay standardization, animal models, immunogenicity, and toxicity testing.
• To discuss clinical evaluation and post-licensing surveillance for new aP vaccines.

Main Areas of Discussion

1. Quality Control Methods

• Current QC relies on product-specific tests, such as antigen characterization, immunogenicity assays, pertussis toxin (PT) residual activity, and endotoxin testing.
• Issues include diversity in vaccine formulations, lack of globally accepted reference standards, and difficulties in assaying immunogenicity.
• Recommendations: Develop internationally harmonized standards, such as JNIH-3 for reference materials, and optimize tests like the histamine sensitization test (HIST) for PT activity.

2. Challenge Models

• Intranasal Challenge Assay (INCA): Demonstrated for monitoring vaccine activity and consistency but not suitable for routine potency release. Proposed improvements include using JNIH-3 as a reference to calculate relative potency.
• Modified Intracerebral Challenge Assay (MICA): Used in some countries for potency testing, with plans to standardize it using JNIH-3. Validity criteria need refinement, and switching to acellular standards is encouraged.

3. Immunogenicity and Toxicity Assays

• Immunogenicity testing monitors production consistency but lacks correlation with protective efficacy. Suggested improvements include establishing stable reference vaccines and validating assays like HPLC and binding assays.
• Toxicity testing involves HIST and endotoxin assays. Challenges include sensitivity variations and limited clinical data linkages. Endotoxin testing needs further study for harmonization.

4. Clinical Evaluation

• New aP vaccines face challenges due to lack of immunological correlates and comparison with historical efficacy data.
• Proposed clinical development strategies: Use non-inferiority studies with control vaccines, and require extensive pre-clinical evaluation for novel antigens. Post-licensing surveillance is essential for real-world effectiveness.

Conclusions and Recommendations

• The working group concluded there is sufficient evidence to revise WHO guidelines and proposed including standardized sections on INCA, MICA, immunogenicity, HIST, and clinical evaluation.
• Key actions: Conduct further collaborative studies, define validity criteria, and encourage the use of reference materials like JNIH-3.
• The outcomes will be presented to the Expert Committee on Biological Standardization in October 2006.

The meeting highlighted the need for global harmonization in vaccine QC to ensure safety, efficacy, and accessibility, particularly for developing countries.