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Fatal enhanced respiratory syncytial virus disease in toddlers. 2021
Fernando P Polack, and
Damián Alvarez-Paggi, and
Romina Libster, and
Mauricio T Caballero, and
Robert V Blair, and
Diego R Hijano, and
Paola X de la Iglesia Niveyro, and
Daniel R Menendez, and
Wes Gladwell, and
Luis M Avendano, and
Luis Velozo, and
Alanna Wanek, and
Eduardo Bergel, and
Gregory A Prince, and
Steven R Kleeberger, and
Joyce Johnson, and
Derek Pociask, and
Jay K Kolls
Fundación INFANT, Buenos Aires, Argentina.
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.
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