๐ A double-inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge
Severe acute respiratory syndrome coronavirus (SARS-CoV) is an important emerging virus that is highly pathogenic in aged populations and is maintained with great diversity in zoonotic reservoirs. While a variety of vaccine platforms have shown efficacy in young-animal models and against homologous viral strains, vaccine efficacy has not been thoroughly evaluated using highly pathogenic variants that replicate the acute end stage lung disease phenotypes seen during the human epidemic. Using an adjuvanted and an unadjuvanted doubleinactivated SARS-CoV (DIV) vaccine, we demonstrate an eosinophilic immunopathology in aged mice comparable to that seen in mice immunized with the SARS nucleocapsid protein, and poor protection against a nonlethal heterologous challenge. In young and 1-year-old animals, we demonstrate that adjuvanted DIV vaccine provides protection against lethal disease in young animals following homologous and heterologous challenge, although enhanced immune pathology and eosinophilia are evident following heterologous challenge. In the absence of alum, DIV vaccine performed poorly in young animals challenged with lethal homologous or heterologous strains. In contrast, DIV vaccines (both adjuvanted and unadjuvanted) performed poorly in aged-animal models. Importantly, aged animals displayed increased eosinophilic immune pathology in the lungs and were not protected against significant virus replication. These data raise significant concerns regarding DIV vaccine safety and highlight the need for additional studies of the molecular mechanisms governing DIV-induced eosinophilia and vaccine failure, especially in the more vulnerable aged-animal models of human disease. ยฉ 2011, American Society for Microbiology.
keywords
๐ syndrome coronavirus (1074)
๐ mice immunized (25)
๐ highly pathogenic (100)
๐ animal models (72)
๐ nucleocapsid protein (162)
๐ virus replication (219)
๐ respiratory syndrome (2004)
๐ acute respiratory (1734)
author
๐ค Bolles, Meagan
๐ค Deming, Damon
๐ค Long, Kristin
๐ค Agnihothram, Sudhakar
๐ค Whitmore, Alan
๐ค Ferris, Martin
๐ค Funkhouser, William
๐ค Gralinski, Lisa
๐ค Totura, Allison
๐ค Heise, Mark
๐ค Baric, Ralph S.
year
โฐ 2011
journal
๐ Journal of Virology
issn
๐ 0022538X 10985514
volume
85
number
23
page
12201-12215
citedbycount
58
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