The antigenic evolution of influenza: drift or thrift?
Wikramaratna, Paul S.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
The Royal Society
© 2013 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.
It is commonly assumed that antibody responses against the influenza virus are polarized in the following manner: strong antibody responses are directed at highly variable antigenic epitopes, which consequently undergo 'antigenic drift', while weak antibody responses develop against conserved epitopes. As the highly variable epitopes are in a constant state of flux, current antibody-based vaccine strategies are focused on the conserved epitopes in the expectation that they will provide some level of clinical protection after appropriate boosting. Here, we use a theoretical model to suggest the existence of epitopes of low variability, which elicit a high degree of both clinical and transmission-blocking immunity. We show that several epidemiological features of influenza and its serological and molecular profiles are consistent with this model of 'antigenic thrift', and that identifying the protective epitopes of low variability predicted by this model could offer a more viable alternative to regularly update the influenza vaccine than exploiting responses to weakly immunogenic conserved regions.
This work was supported by the European Research Council (ERC Advanced Grant—Diversity). M.R. is a Royal Society University Research Fellow, and S.G. is a Royal Society Wolfson Research Fellow.
Research Support, Non-U.S. Gov't
Phil. Trans. R. Soc. B 2013 368 20120200
Place of publication