Research ArticleInfluenza

Cross-Neutralization of 1918 and 2009 Influenza Viruses: Role of Glycans in Viral Evolution and Vaccine Design

Science Translational Medicine  24 Mar 2010:
Vol. 2, Issue 24, pp. 24ra21
DOI: 10.1126/scitranslmed.3000799

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Remembrance of Flus Past

For those who hate needles, this past winter was not a good one. Not only did we have to get the usual seasonal flu shot, doctors recommended that we also get a second shot against another type of flu, a pandemic virus called 2009 H1N1. As the U.S. Centers for Disease Control warned, “A seasonal vaccine will not protect you against 2009 H1N1.” Also odd was the fact that the 2009 H1N1 pandemic flu seemed to spare older people; those age 65 and older were not considered at high risk as they are for seasonal flu. Wei et al. have now worked out why the 2009 H1N1 pandemic flu has these properties, showing how the virus is different from seasonal flu virus but similar to the pandemic flu that swept the globe in 1918. The authors injected mice with seasonal flu viruses as well as with pandemic viruses from 1918 and 2009. The resulting antibodies raised in the mice could inhibit both pandemic viruses in culture and protected mice from infection with either 2009 or 1918 pandemic flu. Antibodies raised to the seasonal flu virus did not have this protective effect, although they protected against seasonal flu perfectly well. In investigating why, Wei et al. found that the key inhibitory antibodies raised to the pandemic flu strains bound to the exposed top of the spike protein, a molecule that projects from the virus and helps it to infect host cells. This immunogenic part of the spike is very similar in the 1918 and 2009 pandemic viruses. Even more interesting is how the seasonal flu escapes from these antibodies. Its spike protein has two sites, not present in the pandemic flu spike protein, to which sugar groups are added, shielding the seasonal flu spike protein from inhibition by the antibodies that act against the pandemic strains. Pandemic flu viruses evolve into seasonal flu varieties, and the authors suggest that one of the key evolutionary steps is the acquisition of the sites for sugar groups on the spike protein. These changes allow the virus to infect people with preexisting immunity to pandemic flu. The results of Wei et al. may also explain the relative resistance of older people to the present flu pandemic: Persistent immunity to the 1918 flu or its close relatives from childhood may inhibit the unprotected spike protein of the current 2009 pandemic flu virus and, thus, its ability to infect host cells.

Footnotes

  • Citation: C.-J. Wei, J. C. Boyington, K. Dai, K. V. Houser, M. B. Pearce, W.-P. Kong, Z-y.. Yang, T. M. Tumpey, G. J. Nabel, Cross-neutralization of 1918 and 2009 influenza viruses: Role of glycans in viral evolution and vaccine design. Sci. Transl. Med. 2, 24ra21 (2010).