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Published Online June 24, 2004
Science DOI: 10.1126/science.1097211

Research Articles

Submitted on ,
Accepted on June 11, 2004

Mapping the Antigenic and Genetic Evolution of Influenza Virus

Derek J. Smith 1*, Alan S. Lapedes 2, Jan C. de Jong 3, Theo M. Bestebroer 3, Guus F. Rimmelzwaan 3, Albert D. M. E. Osterhaus 3, Ron A. M. Fouchier 3

1 Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK; National Influenza Center and Department of Virology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015GE Rotterdam, Netherlands.
2 Theoretical division, T-13, MS B213, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
3 National Influenza Center and Department of Virology, Erasmus Medical Center, Dr. Molewaterplein 50, 3015GE Rotterdam, Netherlands.

* To whom correspondence should be addressed.
Derek J. Smith , E-mail: dsmith{at}zoo.cam.ac.uk

The antigenic evolution of influenza A (H3N2) virus was quantified and visualized from its introduction into humans in 1968 through to 2003. Although there was remarkable correspondence between antigenic and genetic evolution, significant differences were observed: antigenic evolution was more punctuated than genetic evolution, and genetic change sometimes had a disproportionately large antigenic effect. The method readily allows monitoring of antigenic differences among vaccine and circulating strains, and thus estimation of the effects of vaccination. Further, this approach offers a route to predicting the relative success of emerging strains, which could be achieved by quantifying the combined effects of population level immune escape and viral fitness on strain evolution.


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