Fatal enhanced respiratory syncytial virus disease in toddlers
Fernando P. Polack, Damián Álvarez-Paggi, Romina Libster, Mauricio T. Caballero, Robert V. Blair, Diego R. Hijano, Paola X De la Iglesia Niveyro, Daniel Menéndez, Wes Gladwell, Luis M. Avendano, Luis Velozo, Alanna Wanek, Eduardo Bergel, Gregory A. Prince, Steven R. Kleeberger, Joyce E. Johnson, Derek Pociask, Jay K. Kolls
Abstract
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.