Measles and Antibody-Dependent Enhancement (ADE): History and Mechanisms

Abstract

Antibody-dependent enhancement (ADE) is an inadequate response to reinfection or vaccination. ADE was described for influenza and dengue fever: patients already exposed are likely to develop a more severe infection when exposed to a virus of another type than the first. Vaccine antibodies also appear to be responsible for an increased risk of severe disease in a naive person. In COVID-19, ADE is likely with antibodies acquired following infection or vaccination. The aggravation of the disease by measles vaccination has been shown for the inactivated virus vaccines. Atypical measles was also described after the live attenuated vaccine (LAV). ADE mechanisms are the penetration into cells of virus-antibody complexes promoted by FcγR or complement receptors and by an imbalance between neutralizing and facilitating antibodies. The role of maternal antibodies in ADE has been suggested after influenza vaccination in piglets. Facilitation of virus entry into the cell by complement fixation and an imbalance between anti-hemagglutinin and anti-fusion protein antibody levels have been suggested as a mechanism for atypical measles after the inactivated vaccine. Antibodies induced by the current LAV can induce ADE in vitro by binding to FcγR and the same imbalance. A recent vaccination campaign during an outbreak and the comparative history of measles before and during the vaccine era may alert to a possible ADE by the current LAV: it could be caused in infants by maternal antibodies and in adults by waning vaccine immunity. Improvement of current LAV or the development of a new type of vaccine could eliminate this phenomenon.