The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform
Jonathan W. Yewdell - One of the best experts on this subject based on the ideXlab platform.
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is it possible to develop a universal influenza virus vaccine outflanking antibody immunodominance on the road to universal influenza vaccination
Cold Spring Harbor Perspectives in Biology, 2018Co-Authors: Davide Angeletti, Jonathan W. YewdellAbstract:Influenza remains a major human pathogen despite seasonal vaccination. At long last, there is energy and resources to develop influenza vaccines that provide more predictable and durable protection. Vaccines based on inducing antibodies to the conserved stem of the viral hemagglutinin (HA) have emerged as leading candidates for broadening population immunity and ultimately limiting Antigenic Drift. Here, we discuss the knowns and unknowns of HA-specific B-cell and antibody responses. In particular, we focus on how immunodominance sculpts antibody responses and drives Antigenic Drift. We propose a number of strategies to overcome immunodominance and improve the breadth and efficacy of antibody responses.
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antibody pressure by a human monoclonal antibody targeting the 2009 pandemic h1n1 virus hemagglutinin drives the emergence of a virus with increased virulence in mice
Mbio, 2012Co-Authors: Christopher D Odonnell, Jonathan W. Yewdell, Leatrice Vogel, Amber Wright, Jens Wrammert, Guimei Li, Megan Mccausland, Naiying Zheng, Rafi Ahmed, Patrick C WilsonAbstract:ABSTRACT In 2009, a novel H1N1 influenza A virus (2009 pH1N1) emerged and caused a pandemic. A human monoclonal antibody (hMAb; EM4C04), highly specific for the 2009 pH1N1 virus hemagglutinin (HA), was isolated from a severely ill 2009 pH1N1 virus-infected patient. We postulated that under immune pressure with EM4C04, the 2009 pH1N1 virus would undergo Antigenic Drift and mutate at sites that would identify the antibody binding site. To do so, we infected MDCK cells in the presence of EM4C04 and generated 11 escape mutants, displaying 7 distinct amino acid substitutions in the HA. Six substitutions greatly reduced MAb binding (K123N, D131E, K133T, G134S, K157N, and G158E). Residues 131, 133, and 134 are contiguous with residues 157 and 158 in the globular domain structure and contribute to a novel pH1N1 antibody epitope. One mutation near the receptor binding site, S186P, increased the binding affinity of the HA to the receptor. 186P and 131E are present in the highly virulent 1918 virus HA and were recently identified as virulence determinants in a mouse-passaged pH1N1 virus. We found that pH1N1 escape variants expressing these substitutions enhanced replication and lethality in mice compared to wild-type 2009 pH1N1 virus. The increased virulence of these viruses was associated with an increased affinity for α2,3 sialic acid receptors. Our study demonstrates that antibody pressure by an hMAb targeting a novel epitope in the Sa region of 2009 pH1N1 HA is able to inadvertently drive the development of a more virulent virus with altered receptor binding properties. This broadens our understanding of Antigenic Drift. IMPORTANCE Influenza viruses accumulate amino acid substitutions to evade the antibody response in a process known as Antigenic Drift, making it necessary to vaccinate against influenza annually. Mapping human monoclonal antibody (hMAb) epitopes is a necessary step towards understanding Antigenic Drift in humans. We defined the specificity of an hMAb that specifically targeted the 2009 pH1N1 virus and describe a novel epitope. In addition, we identified a previously unappreciated potential for antibody escape to enhance the pathogenicity of a virus. The escape mutation that we identified with in vitro immune pressure was independently reported by other investigators using in vivo selection in nonimmune mice. Although in vitro generation of escape mutants is unlikely to recapitulate Antigenic Drift in its entirety, the data demonstrate that pressure by a human monoclonal antibody targeting a novel epitope in the hemagglutinin of the 2009 pandemic H1N1 virus can inadvertently drive the development of escape mutants, of which a subset have increased virulence and altered receptor binding properties.
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viva la revolucion rethinking influenza a virus Antigenic Drift
Current Opinion in Virology, 2011Co-Authors: Jonathan W. YewdellAbstract:Rapid Antigenic evolution of the influenza A virus hemagglutinin has precluded developing vaccines that provide durable protection. The yearly costs of influenza (circa $1011 in the USA alone) easily justify investments in better understanding the interaction of influenza with antibodies and other inducible elements of the immune system that potentially limit or circumvent Antigenic variation. Here, I summarize exciting new findings that offer the possibility of a quantum improvement in vaccine efficacy, focusing on studies clearly documenting robust neutralizing antibody responses to the conserved stem region of the hemagglutinin.
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glycosylation focuses sequence variation in the influenza a virus h1 hemagglutinin globular domain
PLOS Pathogens, 2010Co-Authors: Suman Das, Pere Puigbo, Scott E Hensley, Darrell E Hurt, Jack R Bennink, Jonathan W. YewdellAbstract:Antigenic Drift in the influenza A virus hemagglutinin (HA) is responsible for seasonal reformulation of influenza vaccines. Here, we address an important and largely overlooked issue in Antigenic Drift: how does the number and location of glycosylation sites affect HA evolution in man? We analyzed the glycosylation status of all full-length H1 subtype HA sequences available in the NCBI influenza database. We devised the “flow index” (FI), a simple algorithm that calculates the tendency for viruses to gain or lose consensus glycosylation sites. The FI predicts the predominance of glycosylation states among existing strains. Our analyses show that while the number of glycosylation sites in the HA globular domain does not influence the overall magnitude of variation in defined Antigenic regions, variation focuses on those regions unshielded by glycosylation. This supports the conclusion that glycosylation generally shields HA from antibody-mediated neutralization, and implies that fitness costs in accommodating oligosaccharides limit virus escape via HA hyperglycosylation.
Suman Das - One of the best experts on this subject based on the ideXlab platform.
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defining influenza a virus hemagglutinin Antigenic Drift by sequential monoclonal antibody selection
Cell Host & Microbe, 2013Co-Authors: Suman Das, Scott E Hensley, William L Ince, Christopher B Brooke, Anju Subba, Mark G Delboy, G Russ, James S GibbsAbstract:Human influenza A virus (IAV) vaccination is limited by “Antigenic Drift,” rapid antibody-driven escape reflecting amino acid substitutions in the globular domain of hemagglutinin (HA), the viral attachment protein. To better understand Drift, we used anti-hemagglutinin monoclonal Abs (mAbs) to sequentially select IAV escape mutants. Twelve selection steps, each resulting in a single amino acid substitution in the hemagglutinin globular domain, were required to eliminate Antigenicity defined by monoclonal or polyclonal Abs. Sequential mutants grow robustly, showing the structural plasticity of HA, although several hemagglutinin substitutions required an epistatic substitution in the neuraminidase glycoprotein to maximize growth. Selecting escape mutants from parental versus sequential variants with the same mAb revealed distinct escape repertoires, attributed to contextual changes in Antigenicity and the mutation landscape. Since each hemagglutinin mutation potentially sculpts future mutation space, Drift can follow many stochastic paths, undermining its unpredictability and underscoring the need for Drift-insensitive vaccines.
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glycosylation focuses sequence variation in the influenza a virus h1 hemagglutinin globular domain
PLOS Pathogens, 2010Co-Authors: Suman Das, Pere Puigbo, Scott E Hensley, Darrell E Hurt, Jack R Bennink, Jonathan W. YewdellAbstract:Antigenic Drift in the influenza A virus hemagglutinin (HA) is responsible for seasonal reformulation of influenza vaccines. Here, we address an important and largely overlooked issue in Antigenic Drift: how does the number and location of glycosylation sites affect HA evolution in man? We analyzed the glycosylation status of all full-length H1 subtype HA sequences available in the NCBI influenza database. We devised the “flow index” (FI), a simple algorithm that calculates the tendency for viruses to gain or lose consensus glycosylation sites. The FI predicts the predominance of glycosylation states among existing strains. Our analyses show that while the number of glycosylation sites in the HA globular domain does not influence the overall magnitude of variation in defined Antigenic regions, variation focuses on those regions unshielded by glycosylation. This supports the conclusion that glycosylation generally shields HA from antibody-mediated neutralization, and implies that fitness costs in accommodating oligosaccharides limit virus escape via HA hyperglycosylation.
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hemagglutinin receptor binding avidity drives influenza a virus Antigenic Drift
Science, 2009Co-Authors: Scott E Hensley, Suman Das, Adam L Bailey, Loren M Schmidt, Heather D Hickman, Akila Jayaraman, Karthik Viswanathan, Rahul Raman, Ram Sasisekharan, Jack R BenninkAbstract:Rapid Antigenic evolution in the influenza A virus hemagglutinin precludes effective vaccination with existing vaccines. To understand this phenomenon, we passaged virus in mice immunized with influenza. Neutralizing antibodies selected mutants with single amino acid hemagglutinin substitutions that increased virus binding to cell surface glycan receptors. Passaging these high avidity-binding mutants in naive mice, but not immune mice, selected for additional hemagglutinin substitutions that decreased cellular receptor binding avidity. Analyzing a panel of monoclonal antibody hemagglutinin escape mutants revealed a positive correlation between receptor binding avidity and escape from polyclonal antibodies. We propose that in response to variation in neutralizing antibody pressure between individuals, influenza A virus evolves by adjusting receptor binding avidity via amino acid substitutions throughout the hemagglutinin globular domain, many of which simultaneously alter Antigenicity.
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hemagglutinin receptor binding avidity drives influenza a virus Antigenic Drift
Science, 2009Co-Authors: Scott E Hensley, Suman Das, Adam L Bailey, Loren M Schmidt, Heather D Hickman, Akila Jayaraman, Karthik Viswanathan, Rahul Raman, Ram Sasisekharan, Jack R BenninkAbstract:Rapid Antigenic evolution in the influenza A virus hemagglutinin precludes effective vaccination with existing vaccines. To understand this phenomenon, we passaged virus in mice immunized with influenza vaccine. Neutralizing antibodies selected mutants with single-amino acid hemagglutinin substitutions that increased virus binding to cell surface glycan receptors. Passaging these high-avidity binding mutants in naive mice, but not immune mice, selected for additional hemagglutinin substitutions that decreased cellular receptor binding avidity. Analyzing a panel of monoclonal antibody hemagglutinin escape mutants revealed a positive correlation between receptor binding avidity and escape from polyclonal antibodies. We propose that in response to variation in neutralizing antibody pressure between individuals, influenza A virus evolves by adjusting receptor binding avidity via amino acid substitutions throughout the hemagglutinin globular domain, many of which simultaneously alter Antigenicity.
David F. Burke - One of the best experts on this subject based on the ideXlab platform.
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Antigenic Drift of the influenza a h1n1 pdm09 virus neuraminidase results in reduced effectiveness of a california 7 2009 h1n1pdm09 specific antibodies
Mbio, 2019Co-Authors: Jin Gao, David F. Burke, Hongquan Wan, Jens Wrammert, Rafi Ahmed, Patrick C Wilson, Laura Couzens, Matthew J. Memoli, Ruth Harvey, Jeffery K TaubenbergerAbstract:The effectiveness of influenza vaccines against circulating A(H1N1)pdm09 viruses was modest for several seasons despite the absence of Antigenic Drift of hemagglutinin (HA), the primary vaccine component. Since antibodies against HA and neuraminidase (NA) contribute independently to protection against disease, Antigenic changes in NA may allow A(H1N1)pdm09 viruses to escape from vaccine-induced immunity. In this study, analysis of the specificities of human NA-specific monoclonal antibodies identified Antigenic sites that have changed over time. The impact of these differences on in vitro inhibition of enzyme activity was not evident for polyclonal antisera until viruses emerged in 2013 without a predicted glycosylation site at amino acid 386 in NA. Phylogenetic and Antigenic cartography demonstrated significant Antigenic changes that in most cases aligned with genetic differences. Typical of NA Drift, the Antigenic difference is observed in one direction, with antibodies against conserved Antigenic domains in A/California/7/2009 (CA/09) continuing to inhibit NA of recent A(H1N1)pdm09 viruses reasonably well. However, ferret CA/09-specific antiserum that inhibited the NA of A/Michigan/45/2015 (MI/15) very well in vitro, protected mice against lethal MI/15 infection poorly. These data show that antiserum against the homologous antigen is most effective and suggest the Antigenic properties of NA should not be overlooked when selecting viruses for vaccine production.IMPORTANCE The effectiveness of seasonal influenza vaccines against circulating A(H1N1)pdm09 viruses has been modest in recent years, despite the absence of Antigenic Drift of HA, the primary vaccine component. Human monoclonal antibodies identified Antigenic sites in NA that changed early after the new pandemic virus emerged. The reactivity of ferret antisera demonstrated Antigenic Drift of A(H1N1)pdm09 NA from 2013 onward. Passive transfer of serum raised against A/California/7/2009 was less effective than ferret serum against the homologous virus in protecting mice against a virus with the NA of more recent virus, A/Michigan/45/2015. Given the long-standing observation that NA-inhibiting antibodies are associated with resistance against disease in humans, these data demonstrate the importance of evaluating NA Drift and suggest that vaccine effectiveness might be improved by selecting viruses for vaccine production that have NAs Antigenically similar to those of circulating influenza viruses.
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The Molecular Basis for Antigenic Drift of Human A/H2N2 Influenza Viruses
Journal of virology, 2019Co-Authors: Martin Linster, David F. Burke, Eefje J. A. Schrauwen, S Van Der Vliet, Pascal Lexmond, Theo M. Bestebroer, Derek J. Smith, Sander Herfst, Björn F. Koel, Ron A. M. FouchierAbstract:Influenza A/H2N2 viruses caused a pandemic in 1957 and continued to circulate in humans until 1968. The Antigenic evolution of A/H2N2 viruses over time and the amino acid substitutions responsible for this Antigenic evolution are not known. Here, the Antigenic diversity of a representative set of human A/H2N2 viruses isolated between 1957 and 1968 was characterized. The Antigenic change of influenza A/H2N2 viruses during the 12 years that this virus circulated was modest. Two amino acid substitutions, T128D and N139K, located in the head domain of the H2 hemagglutinin (HA) molecule, were identified as important determinants of Antigenic change during A/H2N2 virus evolution. The rate of A/H2N2 virus Antigenic evolution during the 12-year period after introduction in humans was half that of A/H3N2 viruses, despite similar rates of genetic change. IMPORTANCE While influenza A viruses of subtype H2N2 were at the origin of the Asian influenza pandemic, little is known about the Antigenic changes that occurred during the twelve years of circulation in humans, the role of preexisting immunity, and the evolutionary rates of the virus. In this study, the Antigenic map derived from hemagglutination inhibition (HI) titers of cell-cultured virus isolates and ferret postinfection sera displayed a directional evolution of viruses away from earlier isolates. Furthermore, individual mutations in close proximity to the receptor-binding site of the HA molecule determined the Antigenic reactivity, confirming that individual amino acid substitutions in A/H2N2 viruses can confer major Antigenic changes. This study adds to our understanding of virus evolution with respect to Antigenic variability, rates of virus evolution, and potential escape mutants of A/H2N2.
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Plasticity of Amino Acid Residue 145 Near the Receptor Binding Site of H3 Swine Influenza A Viruses and Its Impact on Receptor Binding and Antibody Recognition.
Journal of virology, 2019Co-Authors: Jefferson Santos, Eugenio J. Abente, Adebimpe O. Obadan, Andrew J. Thompson, Lucas Ferreri, Ginger Geiger, Ana S. Gonzalez-reiche, Nicola S. Lewis, David F. Burke, Daniela RajaoAbstract:The hemagglutinin (HA), a glycoprotein on the surface of influenza A virus (IAV), initiates the virus life cycle by binding to terminal sialic acid (SA) residues on host cells. The HA gradually accumulates amino acid substitutions that allow IAV to escape immunity through a mechanism known as Antigenic Drift. We recently confirmed that a small set of amino acid residues are largely responsible for driving Antigenic Drift in swine-origin H3 IAV. All identified residues are located adjacent to the HA receptor binding site (RBS), suggesting that substitutions associated with Antigenic Drift may also influence receptor binding. Among those substitutions, residue 145 was shown to be a major determinant of Antigenic evolution. To determine whether there are functional constraints to substitutions near the RBS and their impact on receptor binding and Antigenic properties, we carried out site-directed mutagenesis experiments at the single-amino-acid level. We generated a panel of viruses carrying substitutions at residue 145 representing all 20 amino acids. Despite limited amino acid usage in nature, most substitutions at residue 145 were well tolerated without having a major impact on virus replication in vitro All substitution mutants retained receptor binding specificity, but the substitutions frequently led to decreased receptor binding. Glycan microarray analysis showed that substitutions at residue 145 modulate binding to a broad range of glycans. Furthermore, Antigenic characterization identified specific substitutions at residue 145 that altered antibody recognition. This work provides a better understanding of the functional effects of amino acid substitutions near the RBS and the interplay between receptor binding and Antigenic Drift.IMPORTANCE The complex and continuous Antigenic evolution of IAVs remains a major hurdle for vaccine selection and effective vaccination. On the hemagglutinin (HA) of the H3N2 IAVs, the amino acid substitution N 145 K causes significant Antigenic changes. We show that amino acid 145 displays remarkable amino acid plasticity in vitro, tolerating multiple amino acid substitutions, many of which have not yet been observed in nature. Mutant viruses carrying substitutions at residue 145 showed no major impairment in virus replication in the presence of lower receptor binding avidity. However, their Antigenic characterization confirmed the impact of the 145 K substitution in antibody immunodominance. We provide a better understanding of the functional effects of amino acid substitutions implicated in Antigenic Drift and its consequences for receptor binding and Antigenicity. The mutation analyses presented in this report represent a significant data set to aid and test the ability of computational approaches to predict binding of glycans and in Antigenic cartography analyses.
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Antigenic Drift of the Influenza A(H1N1)pdm09 Virus Neuraminidase Results in Reduced Effectiveness of A/California/7/2009 (H1N1pdm09)-Specific Antibodies
American Society for Microbiology, 2019Co-Authors: Jin Gao, David F. Burke, Hongquan Wan, Jens Wrammert, Laura Couzens, Patrick Wilson, Matthew J. Memoli, Ruth Harvey, Rafi AhmedAbstract:The effectiveness of seasonal influenza vaccines against circulating A(H1N1)pdm09 viruses has been modest in recent years, despite the absence of Antigenic Drift of HA, the primary vaccine component. Human monoclonal antibodies identified Antigenic sites in NA that changed early after the new pandemic virus emerged. The reactivity of ferret antisera demonstrated Antigenic Drift of A(H1N1)pdm09 NA from 2013 onward. Passive transfer of serum raised against A/California/7/2009 was less effective than ferret serum against the homologous virus in protecting mice against a virus with the NA of more recent virus, A/Michigan/45/2015. Given the long-standing observation that NA-inhibiting antibodies are associated with resistance against disease in humans, these data demonstrate the importance of evaluating NA Drift and suggest that vaccine effectiveness might be improved by selecting viruses for vaccine production that have NAs Antigenically similar to those of circulating influenza viruses.The effectiveness of influenza vaccines against circulating A(H1N1)pdm09 viruses was modest for several seasons despite the absence of Antigenic Drift of hemagglutinin (HA), the primary vaccine component. Since antibodies against HA and neuraminidase (NA) contribute independently to protection against disease, Antigenic changes in NA may allow A(H1N1)pdm09 viruses to escape from vaccine-induced immunity. In this study, analysis of the specificities of human NA-specific monoclonal antibodies identified Antigenic sites that have changed over time. The impact of these differences on in vitro inhibition of enzyme activity was not evident for polyclonal antisera until viruses emerged in 2013 without a predicted glycosylation site at amino acid 386 in NA. Phylogenetic and Antigenic cartography demonstrated significant Antigenic changes that in most cases aligned with genetic differences. Typical of NA Drift, the Antigenic difference is observed in one direction, with antibodies against conserved Antigenic domains in A/California/7/2009 (CA/09) continuing to inhibit NA of recent A(H1N1)pdm09 viruses reasonably well. However, ferret CA/09-specific antiserum that inhibited the NA of A/Michigan/45/2015 (MI/15) very well in vitro, protected mice against lethal MI/15 infection poorly. These data show that antiserum against the homologous antigen is most effective and suggest the Antigenic properties of NA should not be overlooked when selecting viruses for vaccine production
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discordant Antigenic Drift of neuraminidase and hemagglutinin in h1n1 and h3n2 influenza viruses
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Matthew R Sandbulte, David F. Burke, Derek J. Smith, Ron A. M. Fouchier, Kim B Westgeest, Jin Gao, Alexander Klimov, Colin A Russell, Maryna C EichelbergerAbstract:Seasonal epidemics caused by influenza virus are driven by Antigenic changes (Drift) in viral surface glycoproteins that allow evasion from preexisting humoral immunity. Antigenic Drift is a feature of not only the hemagglutinin (HA), but also of neuraminidase (NA). We have evaluated the Antigenic evolution of each protein in H1N1 and H3N2 viruses used in vaccine formulations during the last 15 y by analysis of HA and NA inhibition titers and Antigenic cartography. As previously shown for HA, genetic changes in NA did not always lead to an Antigenic change. The noncontinuous pattern of NA Drift did not correspond closely with HA Drift in either subtype. Although NA Drift was demonstrated using ferret sera, we show that these changes also impact recognition by NA-inhibiting antibodies in human sera. Remarkably, a single point mutation in the NA of A/Brisbane/59/2007 was primarily responsible for the lack of inhibition by polyclonal antibodies specific for earlier strains. These data underscore the importance of NA inhibition testing to define Antigenic Drift when there are sequence changes in NA.
E C J Claas - One of the best experts on this subject based on the ideXlab platform.
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Antigenic and molecular heterogeneity in recent swine influenza a h1n1 virus isolates with possible implications for vaccination policy
Vaccine, 2001Co-Authors: J C De Jong, Theo M. Bestebroer, A P Van Nieuwstadt, W L A Loeffen, K Bijlsma, C Verweij, A D M E Osterhaus, E C J Claas, P P Heinen, Guus F RimmelzwaanAbstract:In order to explore the occurrence of Antigenic Drift in swine influenza A(H1N1) viruses and the match between epidemic and vaccine strains, 26 virus isolates from outbreaks of respiratory disease among finishing pigs in the Netherlands in the 1995/1996 season and reference strains from earlier outbreaks were examined using serological and molecular methods. In contrast to swine H3N2 viruses, no significant Antigenic Drift was observed in swine H1N1 viruses isolated from the late 1980s up to 1996 inclusive. However, a marked Antigenic and genetic heterogeneity in haemagglutination inhibition tests and nucleotide sequence analyses was detected among the 26 recent swine H1N1 virus strains. Interestingly, the observed Antigenic and molecular variants were not randomly distributed over the farms. This finding indicates independent introductions of different swine H1N1 virus variants at the various farms of the study and points to a marked difference between the epidemiologies of human and swine influenza viruses. The observed heterogeneity may hamper the control of swine influenza by vaccination and indicates that the efficacy of current swine influenza vaccines requires re-evaluation and that the Antigenic reactivity of swine influenza viruses should be monitored on a regular basis.
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Antigenic Drift in swine influenza h3 haemagglutinins with implications for vaccination policy
Vaccine, 1999Co-Authors: J C De Jong, Theo M. Bestebroer, A P Van Nieuwstadt, T G Kimman, W L A Loeffen, K Bijlsma, C Verweij, A D M E Osterhaus, E C J ClaasAbstract:In order to explore the occurrence of Antigenic Drift in swine influenza A(H3N2) virus, we examined virus strains from outbreaks of respiratory disease among finishing pigs in the Netherlands in 1996 and 1997 and from earlier outbreaks. In contrast to swine H3N2 strains from the 1980s, the recent isolates did not show significant cross-reactivity with human influenza A(H3N2) viruses from 1972-1975 in haemagglutination inhibition tests. These new strains form a separate branch in the phylogenetic trec of the HA1 parts of HA. We conclude that recently there has been considerable Antigenic Drift within the swine H3N2 viruses in the Netherlands and Belgium and recommend replacement of the A/Port Chalmers/1/73 (H3N2) strain in the current vaccine by a more recent swine H3N2 isolate.
J C De Jong - One of the best experts on this subject based on the ideXlab platform.
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Antigenic and molecular heterogeneity in recent swine influenza a h1n1 virus isolates with possible implications for vaccination policy
Vaccine, 2001Co-Authors: J C De Jong, Theo M. Bestebroer, A P Van Nieuwstadt, W L A Loeffen, K Bijlsma, C Verweij, A D M E Osterhaus, E C J Claas, P P Heinen, Guus F RimmelzwaanAbstract:In order to explore the occurrence of Antigenic Drift in swine influenza A(H1N1) viruses and the match between epidemic and vaccine strains, 26 virus isolates from outbreaks of respiratory disease among finishing pigs in the Netherlands in the 1995/1996 season and reference strains from earlier outbreaks were examined using serological and molecular methods. In contrast to swine H3N2 viruses, no significant Antigenic Drift was observed in swine H1N1 viruses isolated from the late 1980s up to 1996 inclusive. However, a marked Antigenic and genetic heterogeneity in haemagglutination inhibition tests and nucleotide sequence analyses was detected among the 26 recent swine H1N1 virus strains. Interestingly, the observed Antigenic and molecular variants were not randomly distributed over the farms. This finding indicates independent introductions of different swine H1N1 virus variants at the various farms of the study and points to a marked difference between the epidemiologies of human and swine influenza viruses. The observed heterogeneity may hamper the control of swine influenza by vaccination and indicates that the efficacy of current swine influenza vaccines requires re-evaluation and that the Antigenic reactivity of swine influenza viruses should be monitored on a regular basis.
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Antigenic Drift in swine influenza h3 haemagglutinins with implications for vaccination policy
Vaccine, 1999Co-Authors: J C De Jong, Theo M. Bestebroer, A P Van Nieuwstadt, T G Kimman, W L A Loeffen, K Bijlsma, C Verweij, A D M E Osterhaus, E C J ClaasAbstract:In order to explore the occurrence of Antigenic Drift in swine influenza A(H3N2) virus, we examined virus strains from outbreaks of respiratory disease among finishing pigs in the Netherlands in 1996 and 1997 and from earlier outbreaks. In contrast to swine H3N2 strains from the 1980s, the recent isolates did not show significant cross-reactivity with human influenza A(H3N2) viruses from 1972-1975 in haemagglutination inhibition tests. These new strains form a separate branch in the phylogenetic trec of the HA1 parts of HA. We conclude that recently there has been considerable Antigenic Drift within the swine H3N2 viruses in the Netherlands and Belgium and recommend replacement of the A/Port Chalmers/1/73 (H3N2) strain in the current vaccine by a more recent swine H3N2 isolate.