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ABSTRACT: Influenza viruses are classic examples of antigenically variable pathogens and have a seemingly endless capacity to evolve in order to evade the immune response. The degree to which immunity induced by one strain is effective against another is mostly dependent on the antigenic difference between the strains. Antigenic drift is thus both the root cause of the enormous public health burden of influenza epidemics, and a primary reason why the virus is such a fascinating pathogen from a scientific perspective. Antigenic cartography is a new technique that can be used to analyse binding assay data and to obtain a detailed quantitative visualization of antigenic differences among pathogens. We provide a brief summary of antigenic cartography and its use to analyse the antigenic drift of influenza A(H3N2) viruses in humans and swine
05/2008: pages 32 - 44; , ISBN: 9780470770672
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Colin A Russell,
Terry C Jones,
Ian G Barr,
Nancy J Cox,
Rebecca J Garten,
Vicky Gregory,
Ian D Gust,
Alan W Hampson,
Alan J Hay,
Aeron C Hurt, [......],
Masatsugu Obuchi,
Takato Odagiri,
Albert D M E Osterhaus,
Guus F Rimmelzwaan,
Michael W Shaw,
Eugene Skepner,
Klaus Stohr,
Masato Tashiro,
Ron A M Fouchier,
Derek J Smith
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ABSTRACT: Antigenic and genetic analysis of the hemagglutinin of approximately 13,000 human influenza A (H3N2) viruses from six continents during 2002-2007 revealed that there was continuous circulation in east and Southeast Asia (E-SE Asia) via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A (H3N2) viruses outside E-SE Asia may be forecast each year based on surveillance within E-SE Asia, with consequent improvements to vaccine strain selection.
Science 05/2008; 320(5874):340-6. · 31.20 Impact Factor
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ABSTRACT: Extract: Annual influenza (flu) epidemics in humans affect 5-15% of the population, causing an estimated half million deaths worldwide per year. Antibodies against the viral surface glycoprotein hemagglutinin (HA) provide protective immunity to influenza virus infection and this protein is therefore the primary component of influenza vaccines. However, the antigenic structure of HA has changed significantly over time, a process known as antigenic drift. In as many years, antigenic drift necessitates an update of the influenza vaccine to ensure sufficient efficacy against newly emerging virus variants. Antigenic drift is therefore both the root cause of the enormous public health burden of influenza epidemics, and a primary reason why the virus is such a fascinating pathogen from a scientific perspective. Thousands of influenza viruses are isolated and analyzed each year by the national and international laboratories that form the World Health Organization (WHO) global influenza surveillance network. This worldwide surveillance effort produces the data for the twice-yearly vaccine strain selection meetings, and has resulted in the establishment of a remarkable historical record of the global evolution of this important pathogen. The degree to which immunity induced by one strain is effective against another is mostly dependent on the extent of the antigenic difference between the strains. The analysis of antigenic differences between strains is therefore critical for surveillance and vaccine strain selection, and is also a cornerstone of basic and applied research in virology.
Discovery medicine 12/2004; 4(24):371-7.
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ABSTRACT: 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.
Science 08/2004; 305(5682):371-6. · 31.20 Impact Factor
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ABSTRACT: In the present study, the recognition of epitope variants of influenza A viruses by human CTL was investigated. To this end, human CD8(+) CTL clones, specific for natural variants of the HLA-B*3501-restricted epitope in the nucleoprotein (NP(418-426)), were generated. As determined in (51)Cr release assays and by flow cytometry with HLA-B*3501-peptide tetrameric complexes, CTL clones were found to be specific for epitopes within one subtype or cross-reactive with heterosubtypic variants of the epitope. Using eight natural variants of the epitope, positions in the 9-mer important for T cell recognition and involved in escape from CTL immunity were identified and visualized using multidimensional scaling. It was shown that positions 4 and 5 in the 9-mer epitope were important determinants of T cell specificity. The in vivo existence of CD8(+) cells cross-reactive with homo- and heterosubtypic variants of the epitope was further confirmed using polyclonal T cell populations obtained after stimulation of PBMC with different influenza A viruses. Based on the observed recognition patterns of the clonal and polyclonal T cell populations and serology, it is hypothesized that consecutive infections with influenza viruses containing different variants of the epitope select for cross-reactive T cells in vivo.
The Journal of Immunology 03/2004; 172(4):2453-60. · 5.79 Impact Factor
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Colin A. Russell,
Terry C. Jones,
Ian G. Barr,
Nancy J. Cox,
Rebecca J. Garten,
Vicky Gregory,
Ian D. Gust,
Alan W. Hampson,
Alan J. Hay,
Aeron C. Hurt, [......],
Masatsugu Obuchi,
Takato Odagiri,
Albert D.M.E. Osterhaus,
Guus F. Rimmelzwaan,
Michael W. Shaw,
Eugene Skepner,
Klaus Stohr,
Masato Tashiro,
Ron A.M. Fouchier,
Derek J. Smith
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[hide abstract]
ABSTRACT: Annual influenza epidemics in humans affect 5–15% of the population, causing an estimated half million deaths worldwide per year [Stohr K. Influenza—WHO cares. Lancet Infectious Diseases 2002;2(9):517]. The virus can infect this proportion of people year after year because the virus has an extensive capacity to evolve and thus evade the immune response. For example, since the influenza A(H3N2) subtype entered the human population in 1968 the A(H3N2) component of the influenza vaccine has had to be updated almost 30 times to track the evolution of the viruses and remain effective. The World Health Organization Global Influenza Surveillance Network (WHO GISN) tracks and analyzes the evolution and epidemiology of influenza viruses for the primary purpose of vaccine strain selection and to improve the strain selection process through studies aimed at better understanding virus evolution and epidemiology. Here we give an overview of the strain selection process and outline recent investigations into the global migration of seasonal influenza viruses.
Vaccine.
