2021-08-30-世界卫生组织-Zika_Virus_Research_and_Development_R_D_Roadmap_54页_1mb

Zika Virus R&D Roadmap Summary - September 2021

Introduction & Vision:
The high-priority goal is to ensure robust medical countermeasures (diagnostics, therapeutics, vaccines) are readily available to detect, prevent, and control Zika virus disease (ZIKV), particularly congenital Zika syndrome (CZS), by 2030. ZIKV, a mosquito-borne flavivirus, causes mild symptoms in adults but poses severe risks, including microcephaly and neurodevelopmental disabilities in congenital infections.

Primary Challenges & Key Needs:

1. Asymptomatic/Mild Infection:

   • ~50–80% of infections are asymptomatic, complicating surveillance and diagnosis.
   • Short incubation (3d–35d) and viremia limit diagnostic window.

2. Cross-Reactivity & Strain Variation:

   • Serological cross-reactivity with other flaviviruses (DENV, WNV) reduces diagnostic accuracy.
   • Limited point-of-care diagnostics and standardization gaps in assays.

3. Congenital Infection Risks:

   • Vertical transmission during pregnancy, genotype variants, and lack of reliable biomarkers for early detection.

4. Outbreak Preparedness:

   • Vector control (e.g., Aedes mosquitoes) and interruptions due to COVID-19 divert resources.

5. Research Gaps:

   • Limited understanding of mechanisms behind CZS, GBS, and potential vaccine-induced enhancement (ADE).

6. Funding & Regulatory Barriers:

   • Declining ZIKV incidence reduces commercial incentives; fragmented regulatory pathways for MCMs.

Strategic Goals & Milestones:

1. Cross-Cutting Issues:

• Develop animal models (e.g., rhesus macaques) and in vitro systems (CHIM) for pathogenesis/studies.
• Standardize diagnostics through international standards and biorepositories.

2. Diagnostics:

• By 2028: Point-of-care tests for early detection and surveillance.
• 2029+ Immunogenic serology (IgA) for immunity assessment.
• Virtual biorepositories (e.g., serum, CSF) for global research.

3. Therapeutics:

• Evaluate monoclonal antibodies (mAbs) and small molecule drugs for maternal infection/prophylaxis.
• 2026+ Preclinical & clinical trials for parenteral routes; address viral persistence in infants.

4. Vaccines:

• Prioritize vaccines targeting pregnancy (2031) & adults (2029).
• Define immune correlates (2028) and leverage alternative regulatory pathways.

4 High-Priority Milestones by Theme:

• Crossing Roadblock: Establish animal models with standardized parameters.
• Diagnostics: Deploy global biorepos for serologic & molecular testing.
• Therapeutics: Complete NHP & clinical trials of mAbs for congenital prevention.
• Vaccines: Secure licensure via expedited pathways for adult/child use.

Conclusion:
A coordinated global effort on diagnostics, therapeutics, and vaccines, supported by robust animal models and equitable deployment, is critical to addressing ZIKV’s public health threat.