Mice vaccinated with the vaccine generated a strong antibody response against M2. In fact, the mice generated a more powerful antibody response to the vaccine than to infections by the flu virus itself, according to Gerhard.

"We saw a significant antibody response to our peptide vaccine," he says. "Actually, the response was much stronger than what we saw in mice recovering from infections, which was surprising. This may be meaningful in terms of the potential effectiveness of the vaccine as we go forward."

The experimental vaccine was administered twice intranasally to mice. After vaccination, a steep rise in M2-specific antibodies was seen in blood samples from the mice, and the mice exhibited significant resistance to viral replication in the respiratory tract.

Ongoing experiments in the Gerhard laboratory are exploring the questions of how and why the new flu vaccine is able to produce a stronger antibody response than infections, which are generally considered the best way to generate resistance to any pathogen.

Also, Gerhard is looking into whether the M2 element of the virus might begin to mutate in the presence of the anti-M2 antibodies generated by the new vaccine. His concern is that the observed viral stability in the M2 region of the flu virus may simply be a reflection of the fact that the immune system does not mount a vigorous response to it, so that evolutionary pressure on that region of the virus is not great.

"Among human influenza virus strains, there is little variation in the M2 region," Gerhard says. "That could be due to the fact that humans do not generate a significant antibody response to it, so that the virus does not need to change to escape those antibodies."

Wistar associate professor Laszlo Otvos, Jr., Ph.D., collaborated on the study. Krystyna Mozdzanowska was the lead author. The remaining coauthors, al
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Contact: Franklin Hoke
hoke@wistar.upenn.edu
215-898-3716
The Wistar Institute
27-May-2003