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. 2004 Nov;78(22):12672-6.
doi: 10.1128/JVI.78.22.12672-12676.2004.

Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets

Hana Weingartl  1 , Markus Czub, Stefanie Czub, James Neufeld, Peter Marszal, Jason Gren, Greg Smith, Shane Jones, Roxanne Proulx, Yvonne Deschambault, Elsie Grudeski, Anton Andonov, Runtao He, Yan Li, John Copps, Allen Grolla, Daryl Dick, Jody Berry, Shelley Ganske, Lisa Manning, Jingxin Cao
Affiliations

Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets

Hana Weingartl et al. J Virol. 2004 Nov.

Abstract

Severe acute respiratory syndrome (SARS) caused by a newly identified coronavirus (SARS-CoV) is a serious emerging human infectious disease. In this report, we immunized ferrets (Mustela putorius furo) with recombinant modified vaccinia virus Ankara (rMVA) expressing the SARS-CoV spike (S) protein. Immunized ferrets developed a more rapid and vigorous neutralizing antibody response than control animals after challenge with SARS-CoV; however, they also exhibited strong inflammatory responses in liver tissue. Inflammation in control animals exposed to SARS-CoV was relatively mild. Thus, our data suggest that vaccination with rMVA expressing SARS-CoV S protein is associated with enhanced hepatitis.

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Figures

FIG. 1.
FIG. 1.
Expression of SARS-CoV S proteins by rMVA-S. The S protein was detected by Western blotting with a SARS-CoV S-specific mouse monoclonal antibody (1). Lane 1, mock-infected BHK21 cell control; lane 2, lysate from MVA-infected BHK21 cells; lane 3, lysate from rMVA-S-infected BHK21 cells.
FIG. 2.
FIG. 2.
ALT level following rMVA-S immunization and SARS-CoV challenge. (A) Prechallenge (ferret 8 sample not available) sample; (B) sample taken 4 to 6 days after infection with SARS-CoV (ferret 3 sample not available); (C) sample taken 13 to 15 days postinfection (dpi; ferret 8 sample not available); (D) sample taken 20 to 22 dpi; (E) sample taken 27 to 29 dpi. ALT values between the dotted scale lines are considered normal reference values.
FIG. 3.
FIG. 3.
Histopathology of ferret livers following immunization and SARS-CoV challenge. Representative pictures were taken at 27 to 29 days postinfection (ferrets [F] 1 to 3, 7 to 9, and 10 to 12) or no infection (naive ferrets 13, 14, and 15; exposed to neither MVA nor SARS-CoV) at ×40 magnification. Perivascular mononuclear infiltrates (red arrows) were present in all livers from ferrets infected with SARS-CoV, ranging from mild (ferrets 1, 2, 3, 10, 11, and 12) to severe (ferrets 7, 8, and 9) lesions. In addition, intralobular infiltration of mononuclear cells was extensive in livers from ferrets 7, 8, and 9. No significant liver lesions were found in naive ferrets (ferrets 13, 14, and 15, which did not receive MVA or SARS-CoV and which were used for preliminary examination of ferrets. Green arrows, vein of portal triads.
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