2022-03-24-世界卫生组织-Advancing_the_development_of_pan-sarbecovirus_vaccines_-_Next_steps_8页_329kb

Summary of "Advancing the development of pan-sarbecovirus vaccines"

Core Content

The World Health Organization (WHO) R&D Blueprint organized a consultation on 25 March 2022 to identify research priorities for the development of pan-sarbecovirus vaccines. This initiative aims to enhance global preparedness against future coronavirus outbreaks by accelerating the creation of vaccines that offer broad protection across multiple sarbecovirus species, including SARS, MERS, and SARS-CoV-2.

Main Objectives

The consultation aimed to:

• Review scientific advances and development approaches for pan-sarbecovirus vaccines.
• Outline novel methods for evaluating these vaccines, especially in the context of variants of concern.
• Discuss strategies for evaluating vaccines against viruses that are not yet circulating.

Why Accelerate Pan-Sarbecovirus Vaccine Development?

• Evolving variants may evade current vaccines, making broad-spectrum vaccines essential.
• Bat reservoirs of beta coronaviruses are large and pose a risk for future zoonotic crossovers.
• Early development can reduce the time needed for large-scale manufacturing and save lives.
• A pan-sarbecovirus vaccine could protect against future variants and new coronaviruses.

Critical Knowledge About Sarbecoviruses

• SARS, MERS, and SARS-CoV-2 cause severe pulmonary disease and have similar clinical features, such as diarrhea and fecal shedding.
• Comorbidities and age increase the risk of severe disease.
• SARS-CoV-2 has lower mortality than MERS or SARS, but long-term effects (Long COVID) are a concern.
• Genetic diversity among sarbecoviruses complicates vaccine development.
• Climate change may influence the emergence of new coronaviruses by altering animal-human interactions.

Vaccine Development Approaches and Challenges

• Key differences among sarbecoviruses (e.g., ACE-2 receptor usage) affect vaccine design.
• Uncertain evolution of SARS-CoV-2 makes it difficult to predict vaccine success.
• Antigenic drift and conserved epitopes are critical for vaccine design.
• Cross-neutralizing antibodies are essential for broad protection.
• Cell-mediated immunity and non-neutralizing humoral responses are important for long-lasting protection.
• Mucosal immunity may play a role in some vaccine strategies.

Vaccine Evaluation Challenges

• Pre-clinical and clinical challenges require focused research.
• Animal models are needed for evaluating vaccine efficacy against multiple viruses.
• Standardized assays and measuring immune responses are vital for regulatory approval.
• Immunobridging and controlled human infection models (CHIM) may be used for evaluation.
• Regulatory harmonization and global coordination are necessary to expedite vaccine deployment.

Ongoing Initiatives

• Major funders such as NIAID, INSERM, and CEPI are investing in new vaccine approaches.
• WHO provides a platform for research coordination and idea exchange.
• Collaborative efforts between regulators and researchers are being fostered to develop WHO guidelines for pan-sarbecovirus vaccines.

Overall Conclusions and Way Forward

• Broadly-specific vaccines are essential for addressing current and future pandemic threats.
• Promising strategies include using conserved antigens, chimeric antigens, and multiple antigens.
• Adjuvants and multi-antigen approaches may enhance immune breadth and efficacy.
• Fewer doses or mucosal administration could improve vaccine deployment.
• WHO is committed to developing a global R&D roadmap for pan-sarbecovirus vaccines, covering basic research to licensure and early use.

Key Steps in the WHO R&D Blueprint Roadmap Development

1. Convene international consultations with diverse experts to gather input.
2. Develop a draft roadmap with support from core subject matter experts.
3. Revise the roadmap with input from an Expert Working Group.
4. Complete a review process by sharing the draft online and incorporating stakeholder feedback.

The roadmap will support both major funders and global academic and industry initiatives to ensure a comprehensive and coordinated approach to vaccine development.