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PLoS Medicine: Mapping Antibody Epitopes of the Avian H5N1 Influenza Virus [Extract]
Mapping Antibody Epitopes of the Avian H5N1 Influenza Virus
Hui-Ling Yen 1, J. S. Malik Peiris 1,2*
1 Department of Microbiology, The University of Hong Kong, University Pathology Building, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China,
2 HKU-Pasteur Research Centre, Hong Kong, Special Administrative Region, People's Republic of China
Citation: Yen H-L, Peiris JSM (2009) Mapping Antibody Epitopes of the Avian H5N1 Influenza Virus. PLoS Med 6(4): e1000064. doi:10.1371/journal.pmed.1000064
Published: April 21, 2009
Copyright: ? 2009 Yen, Peiris. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors' research is supported by the Area of Excellence Scheme of the University Grants Committee (Grant AoE/M-12/06), Hong Kong. The funder played no role in the decision to submit this article or in its preparation.
Competing interests: JSMP is a co-author of one of the studies, cited as reference [25], discussed in this Perspective.
Abbreviations: HA, hemagglutinin; NA, neuraminidase
* E-mail: malik@hkucc.hku.hk
Provenance: Commissioned; not externally peer reviewed
Linked Research Article
This Perspective discusses the following new study published in PLoS Medicine:Khurana S, Suguitan AL Jr., Rivera Y, Simmons CP, Lanzavecchia A, et al. (2009) Antigenic fingerprinting of H5N1 avian influenza using convalescent sera and monoclonal antibodies reveals potential vaccine and diagnostic targets. PLoS Med 6(4): e1000049. doi:10.1371/journal.pmed.1000049
Using whole-genome-fragment phage display libraries, Hana Golding and colleagues identify the viral epitopes recognized by serum antibodies in humans who have recovered from infection with H5N1 avian influenza.
Glossary
Random peptide phage display library: A technique that can be used to select peptide ligands binding to a target molecule (peptide, protein [e.g., antibody], DNA, or RNA). A library of bacteriophages each expressing a random peptide (e.g., 12 mers) fused to the bacteriophage surface proteins is generated.
Bacteriophages that specifically bind to the target molecule are purified through repeated cycles of binding and elution, and the inserts are PCR amplified and sequenced to deduce the peptide that binds to the target molecule. In the paper by Golding et al., this strategy was used to identify the viral epitopes (peptide sequences) recognized by two monoclonal antibodies targeting the H5N1 HA. This method provides fine mapping of antibody epitope to short peptide sequence as compared to the whole-genome-fragment phage display libraries (see below).
Whole-genome-fragment phage display libraries: Instead of using random peptides, the cDNA corresponding to the whole genome of a 2004 human H5N1 influenza isolate was used to construct the phage display library. In the study by Golding et al., cDNA of size ranges of 50?200 or 200?1,000 bp was used to construct the phage display library. Convalescent sera from patients with H5N1 disease were used to probe this phage display library, and the virus epitopes binding specific antibodies were identified.
Clade 1 H5N1 influenza virus: Phylogenetic analysis of the HA gene of highly pathogenic avian influenza H5N1 viruses has led to the subdivision of these viruses into ten virus clades. Phylogenetic trees are like family trees, and a clade of viruses are a group of viruses that are more closely related genetically. The different genetic clades of virus are generally, but not invariably, antigenically distinct, and these differences are relevant in designing vaccines and in assessing vaccine cross-protection.
Antibodies are a major component of specific immune protection against influenza and remain the established immune correlate of protection for influenza vaccines. The importance of humoral immunity against influenza infection is further highlighted by the apparent success of passive immunotherapy with convalescent sera during the 1918 Spanish influenza pandemic, and more recently by anecdotal reports of treating H5N1 human infection with convalescent sera [1], [2].
Human monoclonal antibodies to H5N1 viruses have been generated from immortalized human memory B cells obtained from patients who recovered from H5N1 disease [3] or with combinational antibody library technologies [4].
Some of these antibodies have broad H5N1 cross-clade reactivity [3], [4] or cross-subtype reactivity to H1 viruses [4], and are effective in suppressing H5N1 virus disease in experimentally infected animals when administered prophylactically or therapeutically [3].
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<cite cite="http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000064">PLoS Medicine: Mapping Antibody Epitopes of the Avian H5N1 Influenza Virus</cite>Hui-Ling Yen 1, J. S. Malik Peiris 1,2*
1 Department of Microbiology, The University of Hong Kong, University Pathology Building, Queen Mary Hospital, Hong Kong, Special Administrative Region, People's Republic of China,
2 HKU-Pasteur Research Centre, Hong Kong, Special Administrative Region, People's Republic of China
Citation: Yen H-L, Peiris JSM (2009) Mapping Antibody Epitopes of the Avian H5N1 Influenza Virus. PLoS Med 6(4): e1000064. doi:10.1371/journal.pmed.1000064
Published: April 21, 2009
Copyright: ? 2009 Yen, Peiris. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors' research is supported by the Area of Excellence Scheme of the University Grants Committee (Grant AoE/M-12/06), Hong Kong. The funder played no role in the decision to submit this article or in its preparation.
Competing interests: JSMP is a co-author of one of the studies, cited as reference [25], discussed in this Perspective.
Abbreviations: HA, hemagglutinin; NA, neuraminidase
* E-mail: malik@hkucc.hku.hk
Provenance: Commissioned; not externally peer reviewed
Linked Research Article
This Perspective discusses the following new study published in PLoS Medicine:Khurana S, Suguitan AL Jr., Rivera Y, Simmons CP, Lanzavecchia A, et al. (2009) Antigenic fingerprinting of H5N1 avian influenza using convalescent sera and monoclonal antibodies reveals potential vaccine and diagnostic targets. PLoS Med 6(4): e1000049. doi:10.1371/journal.pmed.1000049
Using whole-genome-fragment phage display libraries, Hana Golding and colleagues identify the viral epitopes recognized by serum antibodies in humans who have recovered from infection with H5N1 avian influenza.
Glossary
Random peptide phage display library: A technique that can be used to select peptide ligands binding to a target molecule (peptide, protein [e.g., antibody], DNA, or RNA). A library of bacteriophages each expressing a random peptide (e.g., 12 mers) fused to the bacteriophage surface proteins is generated.
Bacteriophages that specifically bind to the target molecule are purified through repeated cycles of binding and elution, and the inserts are PCR amplified and sequenced to deduce the peptide that binds to the target molecule. In the paper by Golding et al., this strategy was used to identify the viral epitopes (peptide sequences) recognized by two monoclonal antibodies targeting the H5N1 HA. This method provides fine mapping of antibody epitope to short peptide sequence as compared to the whole-genome-fragment phage display libraries (see below).
Whole-genome-fragment phage display libraries: Instead of using random peptides, the cDNA corresponding to the whole genome of a 2004 human H5N1 influenza isolate was used to construct the phage display library. In the study by Golding et al., cDNA of size ranges of 50?200 or 200?1,000 bp was used to construct the phage display library. Convalescent sera from patients with H5N1 disease were used to probe this phage display library, and the virus epitopes binding specific antibodies were identified.
Clade 1 H5N1 influenza virus: Phylogenetic analysis of the HA gene of highly pathogenic avian influenza H5N1 viruses has led to the subdivision of these viruses into ten virus clades. Phylogenetic trees are like family trees, and a clade of viruses are a group of viruses that are more closely related genetically. The different genetic clades of virus are generally, but not invariably, antigenically distinct, and these differences are relevant in designing vaccines and in assessing vaccine cross-protection.
Antibodies are a major component of specific immune protection against influenza and remain the established immune correlate of protection for influenza vaccines. The importance of humoral immunity against influenza infection is further highlighted by the apparent success of passive immunotherapy with convalescent sera during the 1918 Spanish influenza pandemic, and more recently by anecdotal reports of treating H5N1 human infection with convalescent sera [1], [2].
Human monoclonal antibodies to H5N1 viruses have been generated from immortalized human memory B cells obtained from patients who recovered from H5N1 disease [3] or with combinational antibody library technologies [4].
Some of these antibodies have broad H5N1 cross-clade reactivity [3], [4] or cross-subtype reactivity to H1 viruses [4], and are effective in suppressing H5N1 virus disease in experimentally infected animals when administered prophylactically or therapeutically [3].
(...)
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