2021-11-10-世界卫生组织-Amendment_to_Annex_5_-_Recommendations_to_assure_the_quality,_safety_and_efficacy_of_live_attenuated_yellow_fever_vaccines, _TRS_No_978_9页_159kb

WHO Amendment to Recommendations on Yellow Fever Vaccines Quality, Safety, and Efficacy

This document amends Annex 5 of the WHO Technical Report Series, No. 978, focusing on testing live attenuated yellow fever vaccines. The key changes revise the methods for assessing viscerotropism, immunogenicity, and neurotropism in non-human primates (Macaca mulatta or fascicularis) to address inconsistencies from previous assessments.

Main Revisions:

• Introduction and Background: The amendment stems from the 2010 Recommendations, which faced technical challenges (e.g., scarce data on test performance, difficulties in collaborative studies, lack of international standards, inconsistencies in scoring, and animal sourcing). A WHO working group was established to consult manufacturers and stakeholders, leading to revised protocols.
• Neurotropism Test: Now includes clinical evaluation (daily monitoring for 30 days with scoring from 0 to 4 based on signs like paresis and lethargy) and histopathological evaluation (examining brain sections for lesions). Clinical scoring may be subjective, but telemetry is encouraged for objectivity. The test requires that neither clinical nor histopathological criteria show significant differences from the reference virus.
• Viscerotropism Test: Assesses circulating virus levels in sera on specific days, with limits on virus titers to ensure safety.
• Immunogenicity Test: Requires that at least 90% of test monkeys develop immunity (based on virus-neutralizing titers) within 30 days.
• Overall Acceptability: Both clinical and histopathological scores must compare favorably to reference virus results for the seed lot to be approved. Any deviation requires further investigation.
• Authors and Acknowledgements: The amendment was drafted by a WHO team and reviewed by expert committees, including feedback from manufacturers and regulators.
• References: Includes citations from prior WHO reports and studies on vaccine safety.