2021-11-28-世界卫生组织-Assays_Animal_Models_-_Outline_of_research_priorities_related_to_the_Omicron_variant_3页_276kb

WHO COVID-19 Assays and Animal Models Working Group Summary: Omicron Variant Research Priorities

Background

The WHO R&D Blueprint Working Groups on COVID-19 Assays and Animal Models, comprising over 600 global scientists, met on November 29, 2021, to address knowledge gaps on the SARS-CoV-2 Omicron variant of concern. The urgency stems from multiple mutations in the spike protein, necessitating rapid evaluation of cross-reactivity, transmissibility, and pathogenicity. Meeting objectives included identifying gaps, facilitating expert access to resources, and establishing collaborative mechanisms for sharing viruses, reagents, and data via platforms like WHO-BioHub.

Key Research Priorities

Experts identified three main knowledge gaps:

• Ability of post-vaccination and convalescent sera to neutralize Omicron.
• Efficacy of current vaccines in preventing mild to severe disease.
• Effectiveness of existing therapeutic approaches, such as monoclonal antibodies, protease inhibitors, and nucleoside analogs, against Omicron.

To address these, the following priorities were outlined:

1. Virus Neutralization: Assess neutralization titers in convalescent, vaccinated, and boosted individuals using live Omicron virus; prioritize serum collection as a public health measure.
2. Pseudovirus Neutralization: Conduct neutralization studies using recombinant pseudoviruses with international standard units.
3. T Cell Assays (ELISPOT): Investigate cross-reactive T cell responses for preventing severe disease.
4. Animal Model Studies: Focus on hamsters and non-human primates to evaluate:
   • Pathogenesis compared to other variants.
   • Cross-protection via passive transfer and challenge studies.
   • Transmission through competition studies.
   • Drug resistance against therapies.
   • Need for vaccine reformulation.

Anticipated Challenges

• Virus Availability: Limited by propagation time, sequencing, permits, and transport restrictions due to global flight bans.
• Sharing Mechanisms: Relies on WHO-BioHub and other repositories (e.g., BEI Resources, EV Ag, NIBSC); Category 3 laboratories required for propagation.
• Standardization: T cell assays and shipping may face delays due to ethical approvals and restrictions on sera and reagents.
• Other Model Dependence: Access issues with viral stocks, sera, vaccines, and therapeutics could hamper studies.