title: Brief History and Characterization of Enhanced Respiratory Syncytial Virus Disease.
abstract: In 1967, infants and toddlers immunized with a formalin-inactivated vaccine against respiratory syncytial virus (RSV) experienced an enhanced form of RSV disease characterized by high fever, bronchopneumonia, and wheezing when they became infected with wild-type virus in the community. Hospitalizations were frequent, and two immunized toddlers died upon infection with wild-type RSV. The enhanced disease was initially characterized as a "peribronchiolar monocytic infiltration with some excess in eosinophils." 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(+) 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. This review provides a succinct analysis of these parameters and explores criteria for assessing the risk of ERD in new vaccine candidates.
authors.affiliation: Fundacion INFANT, Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
authors.forename: Patricio L
authors.initials: PL
authors.lastname: Acosta
authors.affiliation: Fundacion INFANT, Buenos Aires, Argentina.
authors.forename: Mauricio T
authors.initials: MT
authors.lastname: Caballero
authors.affiliation: Fundacion INFANT, Buenos Aires, Argentina Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA fernando.p.polack@vanderbilt.edu.
authors.forename: Fernando P
authors.initials: FP
authors.lastname: Polack
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology*; D002675:Child, Preschool; D004802:Eosinophilia / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007223:Infant; D008168:Lung / Q000473:pathology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology*; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014611:Vaccination / Q000009:adverse effects*
chemical_list: D000914:Antibodies, Viral; D022261:Respiratory Syncytial Virus Vaccines