Giuseppe
Emeritus
PLoS Medicine: Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets
Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets
Surender Khurana 1, Amorsolo L. Suguitan, Jr. 2, Yonaira Rivera 1, Cameron P. Simmons 3, Antonio Lanzavecchia 4, Federica Sallusto 4, Jody Manischewitz 1, Lisa R. King 1, Kanta Subbarao 2, Hana Golding1*
1 Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Bethesda, Maryland, United States of America,
2 Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America,
3 Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam,
4 Institute for Research in Biomedicine, Bellinzona, Switzerland
Abstract
Background
Transmission of highly pathogenic avian H5N1 viruses from poultry to humans have raised fears of an impending influenza pandemic. Concerted efforts are underway to prepare effective vaccines and therapies including polyclonal or monoclonal antibodies against H5N1. Current efforts are hampered by the paucity of information on protective immune responses against avian influenza. Characterizing the B cell responses in convalescent individuals could help in the design of future vaccines and therapeutics.
Methods and Findings
To address this need, we generated whole-genome?fragment phage display libraries (GFPDL) expressing fragments of 15?350 amino acids covering all the proteins of A/Vietnam/1203/2004 (H5N1). These GFPDL were used to analyze neutralizing human monoclonal antibodies and sera of five individuals who had recovered from H5N1 infection. This approach led to the mapping of two broadly neutralizing human monoclonal antibodies with conformation-dependent epitopes. In H5N1 convalescent sera, we have identified several potentially protective H5N1-specific human antibody epitopes in H5 HA[(-10)-223], neuraminidase catalytic site, and M2 ectodomain. In addition, for the first time to our knowledge in humans, we identified strong reactivity against PB1-F2, a putative virulence factor, following H5N1 infection. Importantly, novel epitopes were identified, which were recognized by H5N1-convalescent sera but did not react with sera from control individuals (H5N1 na?ve, H1N1 or H3N2 seropositive).
Conclusion
This is the first study, to our knowledge, describing the complete antibody repertoire following H5N1 infection. Collectively, these data will contribute to rational vaccine design and new H5N1-specific serodiagnostic surveillance tools.
Citation: 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
Editor: Malik Peiris, The University of Hong Kong, Hong Kong
Received: November 17, 2008; Accepted: February 12, 2009; Published: April 21, 2009
This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
Funding: This study was partly supported by funds from OPHEMC/HHS (2007) and BARDA/HHS (2008). This research was supported by the Intramural Research Program of CBER (FDA) and NIAID (NIH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: aa, amino acid; AIV, avian influenza viruses; CDC, Centers for Disease Control; GFPDL, whole-genome?fragment phage display libraries; HA, haemagglutinin; HP, highly pathogenic; M2e, M2 ectodomain; MAb, human monoclonal antibodies; NA, neuraminidase; RBS, receptor binding site; RPL, random peptide phage display library; RT, room temperature
* E-mail: hana.golding@fda.hhs.gov
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<cite cite="http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000049">PLoS Medicine: Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets</cite>Surender Khurana 1, Amorsolo L. Suguitan, Jr. 2, Yonaira Rivera 1, Cameron P. Simmons 3, Antonio Lanzavecchia 4, Federica Sallusto 4, Jody Manischewitz 1, Lisa R. King 1, Kanta Subbarao 2, Hana Golding1*
1 Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, Bethesda, Maryland, United States of America,
2 Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America,
3 Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam,
4 Institute for Research in Biomedicine, Bellinzona, Switzerland
Abstract
Background
Transmission of highly pathogenic avian H5N1 viruses from poultry to humans have raised fears of an impending influenza pandemic. Concerted efforts are underway to prepare effective vaccines and therapies including polyclonal or monoclonal antibodies against H5N1. Current efforts are hampered by the paucity of information on protective immune responses against avian influenza. Characterizing the B cell responses in convalescent individuals could help in the design of future vaccines and therapeutics.
Methods and Findings
To address this need, we generated whole-genome?fragment phage display libraries (GFPDL) expressing fragments of 15?350 amino acids covering all the proteins of A/Vietnam/1203/2004 (H5N1). These GFPDL were used to analyze neutralizing human monoclonal antibodies and sera of five individuals who had recovered from H5N1 infection. This approach led to the mapping of two broadly neutralizing human monoclonal antibodies with conformation-dependent epitopes. In H5N1 convalescent sera, we have identified several potentially protective H5N1-specific human antibody epitopes in H5 HA[(-10)-223], neuraminidase catalytic site, and M2 ectodomain. In addition, for the first time to our knowledge in humans, we identified strong reactivity against PB1-F2, a putative virulence factor, following H5N1 infection. Importantly, novel epitopes were identified, which were recognized by H5N1-convalescent sera but did not react with sera from control individuals (H5N1 na?ve, H1N1 or H3N2 seropositive).
Conclusion
This is the first study, to our knowledge, describing the complete antibody repertoire following H5N1 infection. Collectively, these data will contribute to rational vaccine design and new H5N1-specific serodiagnostic surveillance tools.
Citation: 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
Editor: Malik Peiris, The University of Hong Kong, Hong Kong
Received: November 17, 2008; Accepted: February 12, 2009; Published: April 21, 2009
This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
Funding: This study was partly supported by funds from OPHEMC/HHS (2007) and BARDA/HHS (2008). This research was supported by the Intramural Research Program of CBER (FDA) and NIAID (NIH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: aa, amino acid; AIV, avian influenza viruses; CDC, Centers for Disease Control; GFPDL, whole-genome?fragment phage display libraries; HA, haemagglutinin; HP, highly pathogenic; M2e, M2 ectodomain; MAb, human monoclonal antibodies; NA, neuraminidase; RBS, receptor binding site; RPL, random peptide phage display library; RT, room temperature
* E-mail: hana.golding@fda.hhs.gov
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