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Vaccines

2C-02 - Preparing for Vaccine Adverse Events of Special Interest-X (AESI-X): a standardized approach applied to novel vaccines

Sunday, August 24, 2025
3:45 PM - 4:00 PM ET
Background: Real-time harmonization of case definitions (CD) for unanticipated or novel “adverse events of special interest-X” (“AESI-X”) associated with new vaccines can be challenging, as seen in the response to signals associated with COVID-19 vaccines (e.g., Thrombotic Thrombocytopenia Syndrome). The ensuing heterogeneity among CDs results in lack of comparability across passive and active vaccine safety surveillance systems. The Coalition for Epidemic Preparedness Innovations aims to make new vaccines available within 100 days of a pandemic. To ensure preparedness for AESI-X, the Brighton Collaboration's Safety Platform for Emergency vACcines (SPEAC) Project creates CDs and other tools to facilitate standardized safety assessments.

Objectives: To facilitate a consensus AESI-X CD Preparedness Plan among key vaccine safety stakeholders to develop standardized CDs for AESI-X early in a response.

Methods: We identified three categories of AESI-X: 1) Known-known (a recognized syndrome previously associated with another vaccine); 2) Known-unknown (a recognized syndrome not known to be associated with a vaccine); 3) Unknown-unknown (a novel or variant syndrome not previously associated with a vaccine). We created a checklist for CD preparation and introduced this concept to a small group of stakeholders from regulatory agencies, academia and health authorities in February 2024. The group then drafted a consensus AESI-X CD Preparedness Plan.

Results: The AESI-X CD Preparedness Plan consists of the following steps: 1) Outreach by the Brighton Collaboration to countries introducing new vaccines; 2) Signal detection and evaluation by relevant stakeholders; 3) CD Working Group formation; 4) Rapid reviews of draft CD and publication; 5) Implementation of AESI-X CD in surveillance and studies; 6) CD revision and updates during the response; 7) Assessment of lessons learned; 8) AESI-X CD Preparedness Plan updates as needed. A key step is routine outreach to countries introducing new vaccines to offer assistance with CD development should they detect an AESI-X.

Conclusions: Developing this consensus process ahead of an AESI-X will facilitate the implementation and assessment of novel vaccines for priority pathogens and other targets, by anticipating and responding to AESI-X using harmonized CDs. Our next steps include broader dissemination of the plan and consultation among additional stakeholders, including regulatory and health agencies in low- and middle-income countries, and increasing awareness of the plan among pharmacovigilance and real-world data systems in countries which may implement these new vaccines.