Key Point:

Two types of SARS vaccines are producing promising results in murine studies. Both inhibit viral replication and induce a strong antibody response.

BETHESDA, MD—Recently, two separate research teams working at the National Institute of Allergy and Infectious Diseases (NIAID) took an important early step in the development of a vaccine against the severe acute respiratory syndrome (SARS) when they tested candidate vaccines in mice. Both groups found that vaccination triggered a robust antibody response and greatly decreased viral replication in mice exposed to the SARS virus.^1,2

SPIKE PROTEIN

One group employed a vaccine consisting of the spike protein that the SARS virus uses to invade cells. Vaccination with this protein should mimic SARS infection closely enough to elicit immunity without causing illness, explained lead investigator Bernard Moss, MD, PhD.

“We delivered the spike protein in a genetically engineered recombinant vector called the modified vaccinia virus Ankara, or MVA,” explained Dr. Moss, Chief of the Laboratory of Viral Diseases at the NIAID. MVA is an attenuated smallpox vaccine that is already known to be safe in humans and has been used in research aimed at developing human immunodeficiency virus vaccines, he pointed out.

Mice were given the candidate vaccine twice; four weeks after giving the second vaccine, the investigators infected the animals with the SARS virus via the nasal route. Although the virus replicated in the nose and lungs of the control mice, the animals that received the candidate vaccine had little or no detectable virus.

Also, the mice displayed high levels of antibodies against the SARS virus within four weeks of vaccination; antibody levels peaked at six weeks but remained elevated thereafter. When serum from a vaccinated mouse was administered to an unvaccinated mouse that was subsequently infected with the SARS virus, it was shown to protect the second mouse against the virus.

This experimental vaccine is not ready for human trials, however. “At this point, we want to try to modify the vaccine to enhance the immune response that it produces,” Dr. Moss related. “We also want to test it in other animal models before going on to a phase I trial.”

DNA FRAGMENTS

His team’s findings are similar to those obtained recently by another team at the NIAID. Yang et al² created a candidate vaccine from DNA fragments encoding the SARS spike protein; they then tested two versions containing different amounts of the DNA fragments. Thirty days after being immunized, the mice were infected with the SARS virus. Both versions of the vaccine induced a strong antibody response to SARS. Compared with a control group of infected mice, the vaccinated mice also showed more than a one million–fold decline in SARS virus replication in the lungs.

—Timothy Begany

References
1. Bisht H, Roberts A, Vogel L, et al. Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice. Proc Natl Acad Sci U S A. 2004 [Epub ahead of print].
2. Yang Z-Y, Kong W-P, Huang Y, et al. A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature. 2004;428:561-564.

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