Second NIAID SARS Vaccine Candidate Helps Mice Fend Off SARS
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, M.D. "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, M.D., Ph.D.
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 Dr. Moss, and it efficiently stimulates both the antibody and
cellular arms of the immune system.
Dr. Moss and his colleagues collaborated in this research with fellow
NIAID scientist Kanta Subbarao, M.D., 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 Dr. Moss, the researchers will begin to selectively
modify the protein in an effort to enhance its immune-stimulating
powers. Meanwhile, work is continuing in Dr. 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. Press releases, fact sheets and other NIAID-related
materials are available on the NIAID Web site at http://www.niaid.nih.gov.
Note: Media may request a copy of the paper by calling the National
Academy of Sciences at 202-334-1310. Ask for manuscript number 01939.
References: 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:
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.