2024-12-04-世界卫生组织-WHO_technical_consultation_on_immune_correlates_of_protection_for_the_evaluation_of_malaria_vaccines_22页_168kb

WHO Technical Consultation on Immune Correlates of Protection for Malaria Vaccines

Meeting Report Summary
Date: 24–25 June 2024

1. Key Conclusions

• No Validated Correlates Exist: No immune correlates of protection against clinical malaria are validated for recommended vaccines (RTS,S/AS01, R21/Matrix-M).
• Research Needs: Promising biomarkers (e.g., anti-CSP IgG, antibody avidity) lack standardized validation and generalizability to children/countries.
• Feasibility of Use: Immune biomarkers can support trials in specific contexts (e.g., lot-to-lot consistency), but caution is needed due to lack of validated correlates.
• Future Priorities:
  1. Assay Harmonization: Standardize assay platforms, protocols, reference materials, and reagents.
  2. Correlate Confirmation: Conduct formal correlate analyses and align research priorities using harmonized statistical methods.
  3. Next-Generation Vaccines: Re-evaluate existing biomarkers for newer vaccines targeting CSP or other stages.

2. Key Challenges

• Generalizability: Data from CHMI studies (malaria-naïve adults) may not apply to children/real-world settings.
• Methodological Limitations: Assay variability, reagent differences, and lack of longitudinal data hinder reliable comparisons.
• Regulatory Use: Immune correlates are permissible but typically require confirmatory clinical endpoints.

3. Priority Research Areas

1. Lot-to-Lot Consistency: Standardize assays to assess product quality for regulatory approval.
2. Half-Dose Regimens: Limited efficacy data; immunogenicity endpoints must be cautiously interpreted.
3. Interchangeability Studies: Immune biomarkers insufficient alone; mixed vaccine schedules require clinical effectiveness data.

4. Recommendations for Future Work

• WHO Action: Facilitate working groups to:
  • Develop universal standards for assays, protocols, and statistical analyses.
  • Map laboratory capacity in endemic countries.
  • Prioritize confirmatory studies in target populations (infants, young children).
• Scientific Community: Advance assay technologies and functional immunology studies to identify robust correlates.

5. Future Directions

• Validate immune correlates across diverse populations and malaria strains.
• Explore cellular biomarkers (T-cell responses) complementing humoral assays.
• Address the need for harmonized platforms to accelerate correlate discovery.

Source: WHO Meeting Report, June 2024