An experimental vaccine based on a critical piece of the SARS virus protects mice from SARS infection, researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, have found. When exposed to the SARS virus, immunized mice produced SARS-specific antibodies, and virus replication was nearly eliminated.
The new report, to be published this week in the Proceedings of the National Academy of Sciences online, is the second from NIAID in recent weeks describing a promising SARS vaccine candidate.
"We now have two candidate vaccines, based on two distinct technologies, shown to be effective against SARS infection in mice," says NIAID Director Anthony S. Fauci, MD. "The animal model employed in both studies was developed by NIAID researchers as well. By taking various approaches to vaccine development, we are making significant research progress against a disease that was unknown little more than a year ago."
SARS is caused by a coronavirus, a family of viruses so named because spikey proteins protrude from the virus's surface, giving the microbe a crown-like appearance. The newly described vaccine is based on the spike (S) protein. Because the virus initiates infection by attaching to and entering cells using its S protein, a vaccine based on this protein should closely mimic natural infection, notes senior author, Bernard Moss, MD, PhD.
Investigators inserted the gene encoding the S protein into a virus called modified vaccinia Ankara (MVA). Neither MVA nor the solitary gene from the SARS virus can cause disease. Instead, MVA simply ferries the SARS gene into the body. First developed as a vaccine against smallpox, MVA has an excellent safety record in humans, says Moss, and it efficiently stimulates both the antibody and cellular arms of the immune system.
Moss and his colleagues collaborated in this research with fellow NIAID scientist Kanta Subbarao, MD, whose lab recently developed the mouse model of SARS infection. In the current study, two groups of eight mice received doses of the MVA/S vaccine, delivered either into nose or as an injection into muscle, four weeks apart. One month after the second immunization, the rodents were exposed to SARS coronavirus via their nasal passages, mimicking the natural route of infection. Two days later, scientists examined the animals' lungs and nasal passages for evidence of SARS coronavirus replication. Almost no virus was seen in the lungs, and virus levels in the nose were greatly diminished. The results were the same regardless of the vaccination method.
The NIAID scientists also tested the blood of immunized mice to determine the level of antibodies that neutralize the virus. Mice immunized with the MVA/S vaccine developed S-specific neutralizing antibodies. Control mice immunized with MVA alone did not develop antibodies and were not protected from SARS infection.
Finally, the investigators determined that immunity to SARS can be passively acquired. Blood serum from MVA/S immunized mice (which contained anti-SARS antibodies) was injected into non-immunized mice. The non-immunized mice could then fend off SARS infection almost as well as vaccinated mice.
Now that the essential role of S protein in a SARS vaccine has been demonstrated, says Moss, the researchers will begin to selectively modify the protein in an effort to enhance its immune-stimulating powers. Meanwhile, work is continuing in Subbarao's lab to develop improved rodent models of SARS. Currently, while mice can be infected with SARS virus, they do not become ill. Thus, the protective value of the experimental vaccine can only be inferred, not shown directly.
NIAID is a component of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.
H Bisht et al. Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice. Proceedings of the National Academy of Sciences 17:6641-46 (2004). DOI: 10.1073/PNAS.040193901.
Z Yang et al. A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature 428:561-64 (2004). DOI: 10.1038/nature02463.
K Subbarao et al. Prior infection and passive transfer of neutralizing antibody prevent replication of severe acute respiratory syndrome coronavirus in the respiratory tract of mice. Journal of Virology 78:10-16 (2004). DOI: 10.1128/JVI.78.7.
Source: National Institutes of Health