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Originally published in Science Express on 24 June 2004
Science 16 July 2004:
Vol. 305. no. 5682, pp. 371 - 376
DOI: 10.1126/science.1097211
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Research Articles

Mapping the Antigenic and Genetic Evolution of Influenza Virus

Derek J. Smith,1,2*{dagger} Alan S. Lapedes,3* Jan C. de Jong,2 Theo M. Bestebroer,2 Guus F. Rimmelzwaan,2 Albert D. M. E. Osterhaus,2 Ron A. M. Fouchier2*

The antigenic evolution of influenza A (H3N2) virus was quantified and visualized from its introduction into humans in 1968 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.

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



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: dsmith{at}zoo.cam.ac.uk

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