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Hospitalizations were frequent, and two immunized toddlers died upon infection with wild-type RSV. The enhanced disease was initially characterized as a \u201cperibronchiolar monocytic infiltration with some excess in eosinophils.\u201d Decades of research defined enhanced RSV disease (ERD) as the result of immunization with antigens not processed in the cytoplasm, resulting in a nonprotective antibody response and CD4<jats:sup>+<\/jats:sup>T helper priming in the absence of cytotoxic T lymphocytes. This response to vaccination led to a pathogenic Th2 memory response with eosinophil and immune complex deposition in the lungs after RSV infection. In recent years, the field of RSV experienced significant changes. Numerous vaccine candidates with novel designs and formulations are approaching clinical trials, defying our previous understanding of favorable parameters for ERD. 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