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. 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.

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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).
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