Fatal enhanced respiratory syncytial virus disease in toddlers

Sci Transl Med. 2021 Oct 20;13(616):eabj7843. doi: 10.1126/scitranslmed.abj7843. Epub 2021 Oct 20.


In 1967, two toddlers immunized with a formalin-inactivated vaccine against respiratory syncytial virus (FIRSV) in the United States died from enhanced RSV disease (ERD), a severe form of illness resulting from aberrant priming of the antiviral immune response during vaccination. Up to 80% of immunized children subsequently exposed to wild-type virus were hospitalized. These events hampered RSV vaccine development for decades. Here, we provide a characterization of the clinical, immunopathological, and transcriptional signature of fatal human ERD, outlining evidence for safety evaluation of RSV vaccines and a framework for understanding disease enhancement for pathogens in general.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • Communicable Diseases*
  • Humans
  • Respiratory Syncytial Virus Infections* / epidemiology
  • Respiratory Syncytial Virus Vaccines*
  • Respiratory Syncytial Viruses


  • Respiratory Syncytial Virus Vaccines