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: 4.65). 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-DeltaE) were studied using hamsters. Hamsters immunized with rSARS-CoV-DeltaE 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-DeltaE-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-DeltaE is an immunogenic and efficacious vaccine in hamsters.

Download full-text


Available from: AJ Roberts, Feb 18, 2015
  • Source
    [Show abstract] [Hide abstract]
    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.
    Virology 08/2008; 376(2):379-89. DOI:10.1016/j.virol.2008.03.005 · 3.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this review, the current state of vaccine development against human severe acute respiratory syndrome (SARS) coronavirus, focusing on recently published data is assessed. We discuss which strategies have been assessed immunologically and which have been evaluated in SARS coronavirus challenge models. We discuss inactivated vaccines, virally and bacterially vectored vaccines, recombinant protein and DNA vaccines, as well as the use of attenuated vaccines. Data regarding the correlates of protection, animal models and the available evidence regarding potential vaccine enhancement of SARS disease are discussed. While there is much evidence that various vaccine strategies against SARS are safe and immunogenic, vaccinated animals still display significant disease upon challenge. Current data suggest that intranasal vaccination may be crucial and that new or combination strategies may be required for good protective efficacy against SARS in humans.
    Expert Review of Vaccines 08/2009; 8(7):887-98. DOI:10.1586/erv.09.43 · 4.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes 3 major envelope proteins: spike (S), membrane (M), and envelope (E). Previous work identified a dibasic endoplasmic reticulum retrieval signal in the cytoplasmic tail of SARS-CoV S that promotes efficient interaction with SARS-CoV M. The dibasic signal was shown to be important for concentrating S near the virus assembly site rather than for direct interaction with M. Here, we investigated the sequence requirements of the SARS-CoV M protein that are necessary for interaction with SARS-CoV S. The SARS-CoV M tail was shown to be necessary for S localization in the Golgi region when the proteins were exogenously coexpressed in cells. This was specific, since SARS-CoV M did not retain an unrelated glycoprotein in the Golgi. Importantly, we found that an essential tyrosine residue in the SARS-CoV M cytoplasmic tail, Y(195), was important for S-M interaction. When Y(195) was mutated to alanine, M(Y195A) no longer retained S intracellularly at the Golgi. Unlike wild-type M, M(Y195A) did not reduce the amount of SARS-CoV S carbohydrate processing or surface levels when the two proteins were coexpressed. Mutating Y(195) also disrupted SARS-CoV S-M interaction in vitro. These results suggest that Y(195) is necessary for efficient SARS-CoV S-M interaction and, thus, has a significant involvement in assembly of infectious virus.
    Journal of Virology 12/2009; 84(4):1891-901. DOI:10.1128/JVI.02458-09 · 4.65 Impact Factor
Show more