"A key to containing pandemic flu viruses is to understand their vulnerabilities and determine whether they can evade immune recognition," says Dr. Nabel. "What we learn about the H1N1 virus that caused the 1918 pandemic is pertinent to other pandemic viruses and to the development of effective and universal vaccines."
Using the genetic sequence information for the 1918 flu virus, Dr. Nabel and his VRC colleagues created plasmids--small strands of DNA designed to express specific characteristics--carrying genes for the virus' hemagglutinin (HA) protein, the surface protein found in all flu viruses that allows the virus to stick to a cell and cause infection. The researchers created two types of plasmids: one to reflect the HA found in the original 1918 flu virus; the other an altered HA protein designed to attenuate (weaken) the virus.
Mice were then injected with a DNA vaccine containing both types of plasmids to determine whether they would generate immune responses to the 1918 virus. The researchers found significant responses both in terms of production of T-cells, the white blood cells critical in the immune system's battle against invading viruses, as well as the production of neutralizing antibodies.
To determine the vaccine's protective effects, the CDC's Dr. Tumpey intranasally exposed a group of mice to live, reconstructed 1918 virus 14 days after they were immunized with the experimental DNA vaccine. All 10 vaccinated mice survived the challenge with the deadly virus. To explore how the vaccine protected the animals, the researchers first depleted other mice of T-cells; however, this had no effect on the immunity of the vaccinated mice to the 1918 virus. In contrast, the researchers discovered that transferring antibody-rich immunoglobulin (IgG) from immunized mice to non-immunized mice resulted in antibody levels in the animals at levels only slightly lower than those
Source:NIH/National Institute of Allergy and Infectious Diseases