Inactivated COVID-19 vaccines: potential concerns of antibody-dependent enhancement and original antigenic sin

Inactivated vaccine is one of the platforms employed in COVID-19 vaccines. Inactivated vaccines have been associated with concerns of antibody-dependent enhancement (ADE) and original antigenic sin (OAS), which are related to non-neutralising or poorly neutralising antibodies against the pathogen. Since inactivated COVID-19 vaccines use whole-SARS-CoV-2 virus as the immunogen, they are expected to generate antibodies against non-spike structural proteins, which are highly conservative across variants of SARS-CoV-2. These antibodies against non-spike structural proteins have found to be largely non-neutralising or poorly neutralising in nature. Hence, inactivated COVID-19 vaccines could possibly be associated with ADE and OAS, especially as novel variants emerge. This article explores the potential concern of ADE and OAS in the context of inactivated COVID-19 vaccine, and outlines the future research directions.