A Role for Immune Complexes in Enhanced Respiratory Syncytial Virus Disease

TLDR

Respiratory syncytial virus is the leading cause of bronchiolitis and viral pneumonia in infants, and a formalin‑inactivated vaccine in the 1960s caused enhanced disease, a mechanism that remains unclear and has delayed vaccine development. We show that immune complexes drive enhanced RSV disease, as evidenced by protection in complement component C3 and B cell–deficient mice and by complement activation in lung tissues from children who experienced vaccine‑enhanced disease.

Abstract

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral pneumonia in infants and young children. Administration of a formalin inactivated vaccine against RSV to children in the 1960s resulted in increased morbidity and mortality in vaccine recipients who subsequently contracted RSV. This incident precluded development of subunit RSV vaccines for infants for over 30 years, because the mechanism of illness was never clarified. An RSV vaccine for infants is still not available. Here, we demonstrate that enhanced RSV disease is mediated by immune complexes and abrogated in complement component C3 and B cell–deficient mice but not in controls. Further, we show correlation with the enhanced disease observed in children by providing evidence of complement activation in postmortem lung sections from children with enhanced RSV disease.