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

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.

Prior Immunization with Severe Acute Respiratory Syndrome (SARS)-Associated Coronavirus (SARS-CoV) Nucleocapsid Protein Causes Severe Pneumonia in Mice Infected with SARS-CoV

“…Thus, the reduced production of both anti-inflammatory cytokines in the mOrVV-NHis-immunized mice after SARS-CoV infection may be related to the severity of the pulmonary inflammation in these mice. Weingartl et al (47) and Czub et al (48) reported that immunization with S protein expressing-recombinant modified VV Ankara (rMVA-S) induced stronger inflammatory responses and focal necrosis in liver tissues after SARSCoV challenge than in control animals. However, the precise mechanism underlying this liver inflammation has not been clarified.…”

Evaluation of a modified vaccinia virus Ankara (MVA)-based candidate pandemic influenza A/H1N1 vaccine in the ferret model

“…However, recombinant vaccinia viruses expressing different foreign viral antigens, including the HA of influenza virus, have been shown to induce protective immunity in ferrets (Jakeman et al, 1989). A recombinant MVA expressing the spike or nucleocapsid protein of severe acute respiratory syndrome (SARS) coronavirus also proved to be immunogenic (Czub et al, 2005;Weingartl et al, 2004). It is therefore unlikely that the differences in protective effectiveness in monkeys and ferrets were related to the species that was used.…”

Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens

“…A recombinant vesicular stomatitis virus (VSV) expressing the SARS-CoV S protein was protective in mice (14) but has not been tested in primates, and the safety of VSV in humans remains to be established. Recombinant modified vaccinia Ankara (MVA) virus expressing SARS-CoV S protein was immunogenic and protective in rodent and primate models (15)(16)(17); however, one group found that the MVA/SARSCoV S-immunized ferrets developed hepatitis upon challenge with SARS-CoV (17). Vaccine constructs based on replication defective human adenovirus type 5 expressing a partial or full-length SARSCoV S protein have been evaluated for immunogenicity in rats and monkeys (18,19), but immunization depends on a high vaccine dose, and safety and protective efficacy remain to be demonstrated.…”