Focus on the Flu

Rolling up your sleeve for a yearly flu jab could become a thing of the past if researchers can develop a long-lasting and broadly protective vaccine.

Flu vaccines act by giving the immune system a preview of certain proteins found on the coat of the flu virus. However, like a fashion diva, influenza virus changes its coat every season. The changes make each year's version of the flu unrecognizable to the immune system, and so immunity to the flu must be reestablished with a new shot every fall. Scientists are searching for less variable flu parts with the goal of using such elements to develop longer lasting vaccines.

One such stable element is a coat protein called M2. At the Wistar Institute in Philadelphia, NIAID grantee Walter Gerhard, M.D., is using mice to test candidate vaccines containing many bioengineered versions of M2. The mice are inoculated through the nose, mimicking the way flu enters the body. Scientists then can compare the vaccine-created immune response with the response that occurs following natural infection. Generally, the immune system reacts more strongly to natural infections than to vaccines. So the scientists were surprised when the opposite occurred in the vaccinated mice.

Dr. Gerhard is examining how long the immunity provided by these vaccines lasts and whether the virus can find a way of evading these vaccines by developing mutations in their M2 proteins.

• This information is based on the article "Induction of influenza type A virus-specific resistance by immunization of mice with a synthetic multiple antigenic peptide vaccine that contains ectodomains of matrix protein 2" in the journal Vaccine.

• Dr. Gerhard's laboratory Web page on the Wistar Institute Web site
  

Gary Van Nest, Ph.D., a researcher at the biotechnology company Dynavax, is looking inside the flu virus to find a relatively stable component for use in a new kind of vaccine. The vaccine candidate combines an internal flu protein that is less likely to be altered through mutation, NP, with a bioengineered molecule called an immunostimulatory DNA sequence, or ISS.

Dr. Van Nest is testing the NP-ISS vaccine in mice that either have or have not previously been infected with influenza virus. He will examine whether the combination vaccine stimulates certain immune system cells that can fend off different influenza A strains.

Moreover, some of the immune cells stimulated by the vaccine will become "memory" cells that may be able to remember flu virus from year to year. Memory cells against an antigen that is less likely to change through mutation, such as NP, may provide broader protection against the flu than memory cells against an antigen that undergoes numerous changes, such as HA. If the vaccine technique succeeds in mice and non-human primate studies, Dr. Van Nest's research plan includes quickly moving the candidate vaccine into human testing.

• More information about the role ISS technology might play in modifying immune responses to disease is in the following paper by Dr. Van Nest and his colleagues: "Novel chimeric immunomodulatory compounds containing short CpG oligodeoxyribonucleotides have differential activities in human cells," in Nucleic Acids Research.