SARS vaccine based on a replication-defective recombinant vesicular stomatitis virus is more potent than one based on a replication-competent vector.

A SARS vaccine based on a live-attenuated vesicular stomatitis virus (VSV) recombinant expressing the SARS-CoV S protein provides long-term protection of immunized mice from SARS-CoV infection (Kapadia, S.U., Rose, J. K., Lamirande, E., Vogel, L., Subbarao, K., Roberts, A., 2005. Long-term protection from SARS coronavirus infection conferred by a single immunization with an attenuated VSV-based vaccine. Virology 340(2), 174-82.). Because it is difficult to obtain regulatory approval of vaccine based on live viruses, we constructed a replication-defective single-cycle VSV vector in which we replaced the VSV glycoprotein (G) gene with the SARS-CoV S gene. The virus was only able to infect cells when pseudotyped with the VSV G protein. We measured the effectiveness of immunization with the single-cycle vaccine in mice. We found that the vaccine given intramuscularly induced a neutralizing antibody response to SARS-CoV that was approximately ten-fold greater than that required for the protection from SARS-CoV infection, and significantly greater than that generated by the replication-competent vector expressing SARS-CoV S protein given by the same route. Our results, along with earlier studies showing potent induction of T-cell responses by single-cycle vectors, indicate that these vectors are excellent alternatives to live-attenuated VSV.

Utility of the aged BALB/c mouse model to demonstrate prevention and control strategies for severe acute respiratory syndrome coronavirus (SARS-CoV).

The causative agent of Severe Acute Respiratory Syndrome (SARS) was identified as a coronavirus (CoV) following the outbreak of 2002-2003. There are currently no licensed vaccines or treatments for SARS-CoV infections. Potential prevention and control strategies that show promise in vitro must be evaluated in animal models. The aged BALB/c mouse model for SARS supports a high level of viral replication in association with clinical illness and disease that mimics SARS in the elderly. We tested two preventive strategies, vaccination and passive transfer of serum antibody, to determine the extent of protection achieved against SARS-CoV challenge in this model. These approaches were able to achieve or induce antibody titers sufficient to reduce viral load, protect from weight loss and reduce or eliminate histopathologic changes in the lungs of aged mice. This study validates the utility of the aged BALB/c mouse model for evaluation of the efficacy of vaccines and immunoprophylaxis.

Long-term protection from SARS coronavirus infection conferred by a single immunization with an attenuated VSV-based vaccine.

Although the recent SARS coronavirus (SARS-CoV) that appeared in 2002 has now been contained, the possibility of re-emergence of SARS-CoV remains. Due to the threat of re-emergence, the overall fatality rate of approximately 10%, and the rapid dispersion of the virus via international travel, viable vaccine candidates providing protection from SARS are clearly needed. We developed an attenuated VSV recombinant (VSV-S) expressing the SARS coronavirus (SARS-CoV) spike (S) protein. In cells infected with this recombinant, S protein was synthesized, glycosylated at approximately 17 Asn residues, and transported via the Golgi to the cell surface. Mice vaccinated with VSV-S developed SARS-neutralizing antibody and were able to control a challenge with SARS-CoV performed at 1 month or 4 months after a single vaccination. We also demonstrated, by passive antibody transfer, that the antibody response induced by the vaccine was sufficient for controlling SARS-CoV infection. A VSV-vectored SARS vaccine could have significant advantages over other SARS vaccine candidates described to date.