Translating known drivers of COVID-19 disease severity to design better SARS-CoV-2 vaccines

The SARS-CoV-2 pandemic has highlighted how an emergent disease can spread globally and how vaccines are once again the most important public health policy to combat infectious disease. Despite promising initial protection, the rise of new viral variants calls into question how effective current SARS-CoV-2 vaccines will be moving forward. Improving on vaccine platforms represents an opportunity to stay ahead of SARS-CoV-2 and keep the human population protected. Many researchers focus on modifying delivery platforms or altering the antigen(s) presented to improve the efficacy of the vaccines. Identifying mechanisms of natural immunity that result in the control of infection and prevent poor clinical outcomes provides an alternative approach to the development of efficacious vaccines. Early and current evidence shows that SARS-CoV-2 infection is marked by potent lung inflammation and relatively diminished antiviral signaling which leads to impaired immune recognition and viral clearance, essentially making SARS-CoV-2 ‘too hot to handle’.