1092. Adenovirus-Based Vaccine Prevents Pneumonia in Ferrets Challenged with the SARS Coronavirus

Abstract

Top of pageAbstract The human severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiologic agent responsible for the spread of the acute respiratory syndrome in Asia and Canada that claimed several human lives in 2003. A ferret model of SARS-CoV infection was used to evaluate the efficacy of an adenovirus-based vaccine. Ferrets infected with a clinical isolate of SARS-CoV via intranasal inhalation developed a syndrome similar to that observed in humans that consisted of fever and clinical signs of toxicity. Virus replicated in lung and was recovered in nasal washes. Patchy but widely disseminated bronchopneumonia developed characterized by infiltration of neutrophils and monocytes. Animals were vaccinated with recombinant adenoviruses expressing the Spike protein of SARS-CoV prior to challenge with SARS-CoV. The most impressive therapeutic results were obtained when the animals were primed with a human adenovirus expressing Spike and boosted with a serologically distinct adenovirus from chimpanzee also expressing the Spike antigen. Following challenge with SARS-CoV the acute fever was lessened and clinical sequalae were diminished. Viral loads in lung and nasal washes were down 6 logs as compared to animals vaccinated with a control vector. There was no evidence of gross lung pathology at necropsy and histological findings were limited to mild focal inflammation in alveolar septa and around some small airways. The same prime boost strategy was also effective in rhesus macaques and resulted in SARS-CoV neutralizing antibody titers of up to 1/2560 and |[gamma]|-INF positive T cells reaching 12,000 SFC per million PBMCs as assessed by ELISPOT. These data indicate that a heterologous adenovirus-based prime boost vaccine strategy could stimulate a strong immunity that may be needed for complete protection against SARS-CoV infection.