Article

A Live Attenuated Severe Acute Respiratory Syndrome Coronavirus Is Immunogenic and Efficacious in Golden Syrian Hamsters

Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
Journal of Virology (Impact Factor: 4.44). 09/2008; 82(15):7721-4. DOI: 10.1128/JVI.00304-08
Source: PubMed

ABSTRACT

The immunogenicity and protective efficacy of a live attenuated vaccine consisting of a recombinant severe acute respiratory
syndrome (SARS) coronavirus lacking the E gene (rSARS-CoV-ΔE) were studied using hamsters. Hamsters immunized with rSARS-CoV-ΔE
developed high serum-neutralizing antibody titers and were protected from replication of homologous (SARS-CoV Urbani) and
heterologous (GD03) SARS-CoV in the upper and lower respiratory tract. rSARS-CoV-ΔE-immunized hamsters remained active following
wild-type virus challenge, while mock-immunized hamsters displayed decreased activity. Despite being attenuated in replication
in the respiratory tract, rSARS-CoV-ΔE is an immunogenic and efficacious vaccine in hamsters.

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Available from: AJ Roberts, Feb 18, 2015
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    • "Weight loss is difficult to assess in hamsters due to the storage of food in large cheek pouches; however, the use of a running wheel with a rotation counter permitted objective measurement of nocturnal activity of these animals. Compared to mock-infected hamsters and preinfection activity levels, SARS-CoV infected hamsters exhibited a greater than 90% reduction in activity (Roberts et al., 2008; Lamirande et al., 2008). This was the first objective measurement of clinical illness in hamsters. "
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    ABSTRACT: Recombinant severe acute respiratory virus (SARS-CoV) variants lacking the group specific genes 6, 7a, 7b, 8a, 8b and 9b (rSARS-CoV-Delta[6-9b]), the structural gene E (rSARS-CoV-DeltaE), and a combination of both sets of genes (rSARS-CoV-Delta[E,6-9b]) have been generated. All these viruses were rescued in monkey (Vero E6) cells and were also infectious for human (Huh-7, Huh7.5.1 and CaCo-2) cell lines and for transgenic (Tg) mice expressing the SARS-CoV receptor human angiotensin converting enzyme-2 (hACE-2), indicating that none of these proteins is essential for the viral cycle. Furthermore, in Vero E6 cells, all the viruses showed the formation of particles with the same morphology as the wt virus, indicating that these proteins do not have a high impact in the final morphology of the virions. Nevertheless, in the absence of E protein, release of virus particles efficacy was reduced. Viruses lacking E protein grew about 100-fold lower than the wt virus in lungs of Tg infected mice but did not grow in the brains of the same animals, in contrast to the rSARS-CoV-Delta[6-9b] virus, which grew almost as well as the wt in both tissues. Viruses lacking E protein were highly attenuated in the highly sensitive hACE-2 Tg mice, in contrast to the minimal rSARS-CoV-Delta[6-9b] and wt viruses. These data indicate that E gene might be a virulence factor influencing replication level, tissue tropism and pathogenicity of SARS-CoV, suggesting that DeltaE attenuated viruses are promising vaccine candidates.
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