CVR - Coronavirus Vaccines R&D Roadmap

Milestone
3.2.g

Adverse events

In progress

Evaluate the pathophysiology of rare adverse events associated with existing SARS-CoV-2 vaccines, and determine the potential risk of similar adverse events with the most promising approaches.

Progress Highlights

There have been several international efforts to monitor vaccine safety, including adverse events associated with COVID-19 vaccines, such as the WHO Global Advisory Committee on Vaccine Safety, the International Network of Special Immunization Services, and the Global Vaccine Data Network.

Surveillance data suggests that women are more prone to anaphylaxis from lipid nanoparticle mRNA COVID-19 vaccines, potentially due to the polyethylene glycol (PEG)-conjugated lipid derivative, present Pfizer-BioNTech and Moderna vaccines. Similar risks may exist in broadly protective vaccines that contain PEG.

Although myocarditis and pericarditis have been reported as adverse events following mRNA COVID-19 vaccines, there is still no clear understanding of the biological mechanisms responsible; however, males and older adolescents appear to be at higher risk for myocarditis following mRNA COVID-19 vaccination. Broadly protective vaccines using the same mRNA technology could have a comparable risk unless modifications are made (e.g., focusing on conserved epitopes without excessive systemic spike protein expression).

Thrombosis with thrombocytopenia syndrome (TTS) has been associated with adenoviral vector COVID-19 vaccines. Incident rates have been estimated at a few cases per 100,000. Although the pathophysiological specifics are unknown, the condition is likely immune-mediated, with vaccine components triggering the formation of autoantibodies against Platelet Factor 4 (PF4), leading to widespread clotting and platelet depletion. Broadly protective vaccines that are adenoviral vector based may carry a similar risk for TTS. 

Abuawwad 2024 found that Guillain-Barré syndrome (GBS) is also a rarely reported adverse event associated primarily with adenoviral vector COVID-19 vaccines. The mechanisms of why the adenoviral vaccines induce GBS is poorly understood, but in general, GBS is known to result from an autoimmune attack on peripheral nerve myelin, usually due to molecular mimicry. Broadly protective vaccines that are adenoviral vector based may carry a similar risk for GBS. Incorporation of potent adjuvants (e.g., MPLA/QS-21) may also increase GBS risk.