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A role for immune complexes in enhanced respiratory syncytial virus disease
Fernando P Polack1, Michael N Teng, Peter L Collins
1Department of Pediatrics, School of Medicine, Bloomberg School of Public Health at Johns Hopkins University, Baltimore, MD 21205, USA. fpolack@jhsph.edu
Insights
Enhanced respiratory syncytial virus (RSV) disease in children is linked to immune complexes and complement activation. This finding may help in developing safe and effective infant RSV vaccines.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Respiratory syncytial virus (RSV) is a major cause of infant respiratory illness.
- A previous RSV vaccine trial in the 1960s led to severe illness and death in children, halting vaccine development for decades.
- The exact mechanism behind this enhanced RSV disease remains unclear.
Purpose of the Study:
- To elucidate the immunological mechanisms underlying enhanced RSV disease.
- To identify potential targets for safe and effective infant RSV vaccines.
Main Methods:
- Utilized mouse models deficient in complement component C3 and B cells.
- Analyzed postmortem lung tissues from children with severe RSV disease.
- Investigated the role of immune complexes in RSV pathogenesis.
Main Results:
- Enhanced RSV disease was mediated by immune complexes.
- Disease severity was reduced in mice lacking complement component C3 and B cells.
- Evidence of complement activation was found in lung tissues of children with enhanced RSV disease.
Conclusions:
- Immune complex formation and complement activation are key drivers of enhanced RSV disease.
- These findings provide critical insights for the development of safe infant RSV vaccines.
- Understanding these mechanisms is crucial for preventing severe outcomes in young children infected with RSV.
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.