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. 2005 Mar 18;23(17-18):2273-9.
doi: 10.1016/j.vaccine.2005.01.033.

Evaluation of modified vaccinia virus Ankara based recombinant SARS vaccine in ferrets

Markus Czub  1 , Hana Weingartl, Stefanie Czub, Runtao He, Jingxin Cao
Affiliations

Evaluation of modified vaccinia virus Ankara based recombinant SARS vaccine in ferrets

Markus Czub et al. Vaccine. .

Abstract

Severe acute respiratory syndrome (SARS) caused by a newly identified coronavirus (SARS-CoV) remains a threat to cause epidemics as evidenced by recent sporadic cases in China. In this communication, we evaluated the efficacy and safety of two SARS vaccine candidates based on the recombinant modified vaccinia Ankara (MVA) expressing SARS-CoV spike or nucleocapsid proteins in ferrets. No clinical signs were observed in all the ferrets challenged with SARS-CoV. On the other hand, vaccination did not prevent SARS-CoV infection in ferrets. In contrast, immunized ferrets (particularly those immunized with rMVA-spike) exhibited significantly stronger inflammatory responses and focal necrosis in liver tissue after SARS-CoV challenge than control animals. Thus, our data suggest that enhanced hepatitis is linked to vaccination with rMVA expressing SARS-CoV antigens.

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Figures

Fig. 1
Fig. 1
Expression of SARS-CoV N and S proteins by rMVA-N and S recombinant viruses determined by immunoblot. Panel A: detection of SARS-CoV nucleocapsid protein (with a human patient serum); panel B: detection of SARS-CoV spike protein (with a SARS-CoV spike specific mouse monoclonal antibody); lane 1: BHK21 cell control, lane 2: rMVA-N infected BHK21 cell lysate, lane 3: rMVA-S infected BHK21 cell lysate.
Fig. 2
Fig. 2
ALT level following rMVA immunization and SARS-CoV challenge. Panel A: pre-challenge (ferret #8 sample not available); panel B: 3–5 days post infection (dpi) with SARS-CoV (ferret #3 sample not available); panel C: 12–14 dpi (ferret #8 sample not available); panel D: 19–21 dpi; panel E: 27–29 dpi; the ALT value between the dotted scale line is considered as normal reference value.
Fig. 3
Fig. 3
Representative pictures of livers from ferrets. Perivascular mononuclear infiltrates were present in all livers from ferrets exposed to SARS-CoV: (A) MVA, mild hepatitis; (B) rMVA-SARS-N; (C) rMVA-SARS-S, severe hepatitis with focal necrosis; (D) PBS control, mild hepatitis; (E) non-infected, no significant lesions. Arrows: vein (green); artery (yellow); and bile duct (green).
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