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In Search of the Flu’s Magic Bullet

If we ever hope to find a less fickle flu vaccine, maybe we need to pick a different target.

Photo of Andrew Pekosz, Ph.D.
Andrew Pekosz, Ph.D.

Andrew Pekosz, Ph.D., assistant professor in the Washington University School of Medicine, St. Louis, MO, and David Milich, Ph.D., an immunologist with the Vaccine Research Institute, San Diego, CA, are setting out to do just that. Drs. Pekosz and Milich are trying to determine if the influenza A virus M2 protein would make a much better target for a flu vaccine than the currently targeted HA and NA surface proteins.

The reason to consider the switch is that HA and NA proteins are always changing (see antigenic shift and antigenic drift). To keep up, we need to be vaccinated against new strains every year.

But the M2 protein in human flu strains remains the same from year to year, and from strain to strain. One vaccine could be all we'd need to remain protected against the variety of human flu viruses. Already, Dr. Pekosz has demonstrated that M2 antibodies can protect mice from a lethal influenza A virus.

One potential drawback to using the M2 protein is far fewer copies of the protein are present on the outer coat of the influenza A virus when compared with the HA and NA proteins, so a vaccine created from a normal flu strain would generate too few M 2 specific-antibodies. But Dr. Milich has a way of getting around this. He has developed a “bulked-up” M2 vaccine—called the M2 protein core—that contains 240 copies of the M2 protein, thus making it capable of stimulating the production of many more antibodies.

The researchers are now studying how well the M2 protein core works, not just against human flu strains, but against bird and pig flu strains as well. (The M2 protein in bird and flu strains is slightly different from that in human strains.) Dr. Milich's lab is preparing M2 protein cores containing human, bird, and pig influenza A strains and studying the immune responses in mice. Dr. Pekosz's lab is testing cross-reactivity between the different species and strains. To do this, they are immunizing mice, and later other animals, with M2 vaccines against human and bird flu strains and then studying their immune responses against both.

If the studies are successful, the M2 protein could prove itself an excellent target for flu protection. But because antibodies against the HA and M2 proteins protect in different ways, Dr. Pekosz wonders if a vaccine against both proteins might be better still, offering two different but complementary levels of protection.

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Last Updated March 23, 2010