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      Using Sequence Data To Infer the Antigenicity of Influenza Virus

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          ABSTRACT

          The efficacy of current influenza vaccines requires a close antigenic match between circulating and vaccine strains. As such, timely identification of emerging influenza virus antigenic variants is central to the success of influenza vaccination programs. Empirical methods to determine influenza virus antigenic properties are time-consuming and mid-throughput and require live viruses. Here, we present a novel, experimentally validated, computational method for determining influenza virus antigenicity on the basis of hemagglutinin (HA) sequence. This method integrates a bootstrapped ridge regression with antigenic mapping to quantify antigenic distances by using influenza HA1 sequences. Our method was applied to H3N2 seasonal influenza viruses and identified the 13 previously recognized H3N2 antigenic clusters and the antigenic drift event of 2009 that led to a change of the H3N2 vaccine strain.

          IMPORTANCE

          This report supplies a novel method for quantifying antigenic distance and identifying antigenic variants using sequences alone. This method will be useful in influenza vaccine strain selection by significantly reducing the human labor efforts for serological characterization and will increase the likelihood of correct influenza vaccine candidate selection.

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          Most cited references36

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          Detection of antibody to avian influenza A (H5N1) virus in human serum by using a combination of serologic assays.

          From May to December 1997, 18 cases of mild to severe respiratory illness caused by avian influenza A (H5N1) viruses were identified in Hong Kong. The emergence of an avian virus in the human population prompted an epidemiological investigation to determine the extent of human-to-human transmission of the virus and risk factors associated with infection. The hemagglutination inhibition (HI) assay, the standard method for serologic detection of influenza virus infection in humans, has been shown to be less sensitive for the detection of antibodies induced by avian influenza viruses. Therefore, we developed a more sensitive microneutralization assay to detect antibodies to avian influenza in humans. Direct comparison of an HI assay and the microneutralization assay demonstrated that the latter was substantially more sensitive in detecting human antibodies to H5N1 virus in infected individuals. An H5-specific indirect enzyme-linked immunosorbent assay (ELISA) was also established to test children's sera. The sensitivity and specificity of the microneutralization assay were compared with those of an H5-specific indirect ELISA. When combined with a confirmatory H5-specific Western blot test, the specificities of both assays were improved. Maximum sensitivity (80%) and specificity (96%) for the detection of anti-H5 antibody in adults aged 18 to 59 years were achieved by using the microneutralization assay combined with Western blotting. Maximum sensitivity (100%) and specificity (100%) in detecting anti-H5 antibody in sera obtained from children less than 15 years of age were achieved by using ELISA combined with Western blotting. This new test algorithm is being used for the seroepidemiologic investigations of the avian H5N1 influenza outbreak.
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            Estimates of deaths associated with seasonal influenza --- United States, 1976-2007.

            David Shay (2010)
            Influenza infections are associated with thousands of deaths every year in the United States, with the majority of deaths from seasonal influenza occurring among adults aged >or=65 years. For several decades, CDC has made annual estimates of influenza-associated deaths, which have been used in influenza research and to develop influenza control and prevention policy. To update previously published estimates of the numbers and rates of influenza-associated deaths during 1976-2003 by adding four influenza seasons through 2006-07, CDC used statistical models with data from death certificate reports. National mortality data for two categories of underlying cause of death codes, pneumonia and influenza causes and respiratory and circulatory causes, were used in regression models to estimate lower and upper bounds for the number of influenza-associated deaths. Estimates by seasonal influenza virus type and subtype were examined to determine any association between virus type and subtype and the number of deaths in a season. This report summarizes the results of these analyses, which found that, during 1976-2007, estimates of annual influenza-associated deaths from respiratory and circulatory causes (including pneumonia and influenza causes) ranged from 3,349 in 1986-87 to 48,614 in 2003-04. The annual rate of influenza-associated death in the United States overall during this period ranged from 1.4 to 16.7 deaths per 100,000 persons. The findings also indicated the wide variation in the estimated number of deaths from season to season was closely related to the particular influenza virus types and subtypes in circulation.
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              Exact and efficient analytical calculation of the accessible surface areas and their gradients for macromolecules

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                Author and article information

                Journal
                mBio
                MBio
                mbio
                mbio
                mBio
                mBio
                American Society of Microbiology (1752 N St., N.W., Washington, DC )
                2150-7511
                2 July 2013
                Jul-Aug 2013
                : 4
                : 4
                : e00230-13
                Affiliations
                Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, USA [ a ]
                Department of Statistics, Rutgers University, Piscataway, New Jersey, USA [ b ]
                Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA [ c ]
                Author notes
                Address correspondence to Xiu-Feng Wan, wan@ 123456cvm.msstate.edu .

                H.S. and J.Y. contributed equally to this work.

                Invited Editor Stanley Perlman, University of Iowa Editor Christine Biron, Brown University

                Article
                mBio00230-13
                10.1128/mBio.00230-13
                3705446
                23820391
                21f5faec-d079-4dbc-8f16-d0133b0274ae
                Copyright © 2013 Sun et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 1 April 2013
                : 10 June 2013
                Page count
                Pages: 9
                Categories
                Research Article
                Custom metadata
                July/August 2013

                Life sciences
                Life sciences

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