Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Apr;133(1):20-32.
doi: 10.1016/j.virusres.2007.03.025. Epub 2007 May 11.

Animal models and vaccines for SARS-CoV infection

Anjeanette Roberts  1 , Elaine W Lamirande, Leatrice Vogel, Jadon P Jackson, Christopher D Paddock, Jeannette Guarner, Sherif R Zaki, Timothy Sheahan, Ralph Baric, Kanta Subbarao
Affiliations

Animal models and vaccines for SARS-CoV infection

Anjeanette Roberts et al. Virus Res. 2008 Apr.

Abstract

We summarize findings of SARS-CoV infections in several animal models each of which support viral replication in lungs accompanied by histopathological changes and/or clinical signs of illness to varying degrees. New findings are reported on SARS-CoV replication and associated pathology in two additional strains (C57BL/6 and 129S6) of aged mice. We also provide new comparative data on viral replication and associated pathology following infection of golden Syrian hamsters with various SARS-CoV strains and report the levels of neutralizing antibody titers following these infections and the cross-protective efficacy of infection with these strains in protecting against heterologous challenge. Finally, we summarize findings of a variety of vaccine approaches and discuss the available in vitro and in vivo data addressing the potential for disease enhancement following re-infection in animals previously vaccinated against or infected with SARS-CoV.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Replication of SARS-CoV in lungs of aged B6 and BALB/c mice. B6 and BALB/c mice (N = 15 per strain, aged 12–14 months) were intranasally infected with SARS-CoV (105 TCID50/mouse) at day 0. Five mice per strain were sacrificed at days 2, 5 and 6 post-infection. Bars (hatched = B6; open = BALB/c) indicate the mean titer of virus detected in 10% (w/v) lung homogenates by 50% tissue culture infectious dose (TCID50) assays on Vero cell monolayers. Error bars indicate standard error. Dashed line indicates limit of detection, 101.5 TCID50/g lung.
Fig. 2
Fig. 2
Histopathologic features of infection with SARS-CoV in the lungs of aged 129S6, B6 and BALB/c mice at 3 days post-infection. (A) Florid perivascular and peribronchiolar inflammatory cell infiltrates comprised predominantly of mononuclear cells (strain 129S6, original magnification 25×). (B) Abundant SARS-CoV antigens (red) in the cytoplasm of bronchiolar epithelial cells (strain 129S6, original magnification 50×). (C) Necrotic respiratory epithelium and inflammatory cells in the lumen of a small pulmonary bronchiole (strain BL6, original magnification 50×). (D) Immunohistochemical staining of the same section in C, showing scattered SARS-CoV antigens in the intraluminal debris. (E) Focus of interstitial inflammatory cell infiltrate (strain BALB/c, original magnification 50×). (F) SARS-CoV antigen in alveolar pneumocytes adjacent to a bronchiole (strain BALB/c, original magnification 50×). Hematoxylin and eosin stain (A, C, E); immunoalkaline phosphatase with naphthol fast-red substrate and hematoxylin counterstain (B, D, F).
Fig. 3
Fig. 3
Primary replication and replication after challenge of SARS-CoV in hamster lungs. Golden Syrian hamsters (50–55 days old) were intranasally inoculated with one of four SARS-CoV strains (A) HK-39 (N = 16), (B) Urbani (N = 16), (C) Frk-1 (N = 16), and (D) icGD03 (N = 12) of SARS-CoV (103 TCID50/hamster). For evaluating viral replication following primary (1°) infection, four hamsters per strain (three hamsters for icGD03) were sacrificed at day 2 post-infection. For evaluation of protection from secondary (2°) infection, the remaining hamsters were challenged 28 days after 1° infection with the indicated homologous or heterologous strain of SARS-CoV (N = 4 per group; or N = 3/group for icGD03; 103 TCID50/hamster) and sacrificed 2 days later. Bars indicate the mean titer of virus detected in 10% (w/v) lung homogenates by TCID50 assay on Vero cells (1° = day 2 after initial infection; 2° = day 2 after challenge). Error bars indicate standard error. Dashed line indicates limit of detection, 101.5 TCID50/g lung.
Fig. 4
Fig. 4
Pathology in lungs of golden Syrian hamsters following SARS-CoV infection. Lungs from SARS-CoV-infected (Urbani, A and B; Frankfurt-1, C and D; HKU-39849, E and D) hamsters at day 5 p.i. show confluent pneumonic consolidation (hematoxylin-and-eosin stain, A, C, and E), and SARS-CoV antigens (IHC assays, antigen in red; B, D, and F) in consolidated areas (asterisk) and bronchial epithelium (arrows). Original magnifications: 25× (A, C and E); 50× (B, D and F).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bisht H., Roberts A., Vogel L., Bukreyev A., Collins P.L., Murphy B.R., Subbarao K., Moss B. Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice. Proc. Natl. Acad. Sci. U.S.A. 2004;101(17):6641–6646. - PMC - PubMed
    1. Bisht H., Roberts A., Vogel L., Subbarao K., Moss B. Neutralizing antibody and protective immunity to SARS coronavirus infection of mice induced by a soluble recombinant polypeptide containing an N-terminal segment of the spike glycoprotein. Virology. 2005;334(2):160–165. - PMC - PubMed
    1. Buchholz U.J., Bukreyev A., Yang L., Lamirande E.W., Murphy B.R., Subbarao K., Collins P.L. Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity. Proc. Natl. Acad. Sci. U.S.A. 2004;101(26):9804–9809. - PMC - PubMed
    1. Bukreyev A., Lamirande E.W., Buchholz U.J., Vogel L.N., Elkins W.R., St Claire M., Murphy B.R., Subbarao K., Collins P.L. Mucosal immunisation of African green monkeys (Cercopithecus aethiops) with an attenuated parainfluenza virus expressing the SARS coronavirus spike protein for the prevention of SARS. Lancet. 2004;363(9427):2122–2127. - PMC - PubMed
    1. Chen Z., Zhang L., Qin C., Ba L., Yi C.E., Zhang F., Wei Q., He T., Yu W., Yu J., Gao H., Tu X., Gettie A., Farzan M., Yuen K.Y., Ho D.D. Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region. J. Virol. 2005;79(5):2678–2688. - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources