Step Toward Vaccination Against Multiple Influenza Strains

Graphical representation of a generic influenza virus particle's structure. CDC/Douglas Jordan, 2009. Illustrator: Dan HigginsInfluenza is a challenging disease for vaccine researchers. At any given time, multiple influenza strains are circulating, and immunity against one strain does not necessarily provide protection against others. In addition, influenza A viruses frequently mutate, so that it is difficult to find a “target” within the virus that will remain stable between various strains and mutations. As a result, the current approach for developing flu vaccines is based on observations of the strains most likely to be circulating in the coming flu season. The seasonal flu vaccine contains three inactivated strains of influenza, but typically can’t provide protection against other strains.

Now, the results of a recent study in mice suggest that a new approach may be able to provide long-lasting, cross-strain protection against influenza. One portion of influenza A viruses that tends to remain fairly stable despite strain mutations is a part of a protein (the so-called M2 protein) on the surface of the influenza virus particle. Because a portion of this protein appears to be the same across many different strains of influenza, it could potentially make a good target for a vaccine against each strain. However, past research has found that the M2 protein is poorly immunogenic — that is, it does not generate a good immune response.

Researchers at the Emory University School of Medicine decided to find out whether the M2 protein could be used in combination with a single killed influenza strain to provide cross-strain protection. To do so, they used “virus-like particles” (VLPs): materials from the outer protein coat of the virus, presenting the M2 protein. (VLPs are also used in the human papillomavirus, or HPV, vaccine.)

One group of mice received a vaccine consisting of a killed strain of H1N1 influenza A virus. Another group received both the killed virus and M2 VLPs; a control group received an unrelated VLP.

The mice were then challenged with a lethal dose of an H3N2 influenza A virus. All of the mice in the control group were infected and died, and mice that had received only the killed strain of H1N1 suffered severe losses in body weight (a sign of disease), although none died. The mice that had received both the killed strain and the M2 VLPs, however, showed no signs of disease at all. The killed virus and VLP combination also provided protection against challenge with H1N1 and H5N1 strains.

Finally, the researchers tested the duration of immunity provided by the combination by challenging the mice with infection seven months after the initial vaccination. Once again, the mice that had received the combination of inactivated influenza and VLPs survived the infection, with no weight loss.

Although this research is preliminary and much more research must be done before the process could be used to provide protection for humans, it is a promising step toward a universal influenza vaccine. If this success can be replicated, the need for a new seasonal flu shot every year could be greatly diminished.

Sources and more information

Song J, Van Rooijen N, Bozja J, Compans RW, and Kang S. Vaccination inducing broad and improved cross protection against multiple subtypes of influenza A virus. PNAS 2010 : 1012199108v1-201012199. http://www.pnas.org/content/early/2010/12/20/1012199108

Fiore K. New Flu Vaccine Cross-Protective in Animal Model. Medpage Today. December 28, 2010. http://www.medpagetoday.com/InfectiousDisease/URItheFlu/24087

CDC: Seasonal Influenza
http://www.cdc.gov/flu/