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Article: Heterosubtypic neutralizing monoclonal antibodies cross-protective against H5N1 and H1N1 recovered from human IgM + memory B cells

TitleHeterosubtypic neutralizing monoclonal antibodies cross-protective against H5N1 and H1N1 recovered from human IgM + memory B cells
Authors
Issue Date2008
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2008, v. 3 n. 12 How to Cite?
AbstractBackground: The hemagglutinin (HA) glycoprotein is the principal target of protective humoral immune responses to influenza virus infections but such antibody responses only provide efficient protection against a narrow spectrum of HA antigenic variants within a given virus subtype. Avian influenza viruses such as H5N1 are currently panzootic and pose a pandemic threat. These viruses are antigenically diverse and protective strategies need to cross protect against diverse viral clades. Furthermore, there are 16 different HA subtypes and no certainty the next pandemic will be caused by an H5 subtype, thus it is important to develop prophylactic and therapeutic interventions that provide heterosubtypic protection. Methods and Findings: Here we describe a panel of 13 monoclonal antibodies (mAbs) recovered from combinatorial display libraries that were constructed from human IgM + memory B cells of recent (seasonal) influenza vaccinees. The mAbs have broad heterosubtypic neutralizing activity against antigenically diverse H1, H2, H5, H6, H8 and H9 influenza subtypes. Restriction to variable heavy chain gene IGHV1-69 in the high affinity mAb panel was associated with binding to a conserved hydrophobic pocket in the stem domain of HA. The most potent antibody (CR6261) was protective in mice when given before and after lethal H5N1 or H1N1 challenge. Conclusions: The human monoclonal CR6261 described in this study could be developed for use as a broad spectrum agent for prophylaxis or treatment of human or avian influenza infections without prior strain characterization. Moreover, the CR6261 epitope could be applied in targeted vaccine strategies or in the design of novel antivirals. Finally our approach of screening the IgM + memory repertoire could be applied to identify conserved and functionally relevant targets on other rapidly evolving pathogens. © 2008 Throsby et al.
Persistent Identifierhttp://hdl.handle.net/10722/59385
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
SenterNovemIS055026
Area of Excellence Scheme of the University Grants Committee, Hong KongAoE/M-12/06
Funding Information:

This work was supported through grant IS055026 from SenterNovem. LLMP, YG and JSMP are supported by an Area of Excellence Scheme of the University Grants Committee, Hong Kong (Grant AoE/M-12/06). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References
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DC FieldValueLanguage
dc.contributor.authorThrosby, Men_HK
dc.contributor.authorvan den Brink, Een_HK
dc.contributor.authorJongeneelen, Men_HK
dc.contributor.authorPoon, LLMen_HK
dc.contributor.authorAlard, Pen_HK
dc.contributor.authorCornelissen, Len_HK
dc.contributor.authorBakker, Aen_HK
dc.contributor.authorCox, Fen_HK
dc.contributor.authorvan Deventer, Een_HK
dc.contributor.authorGuan, Yen_HK
dc.contributor.authorCinatl, Jen_HK
dc.contributor.authorter Meulen, Jen_HK
dc.contributor.authorLasters, Ien_HK
dc.contributor.authorCarsetti, Ren_HK
dc.contributor.authorPeiris, Men_HK
dc.contributor.authorde Kruif, Jen_HK
dc.contributor.authorGoudsmit, Jen_HK
dc.date.accessioned2010-05-31T03:49:02Z-
dc.date.available2010-05-31T03:49:02Z-
dc.date.issued2008en_HK
dc.identifier.citationPlos One, 2008, v. 3 n. 12en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59385-
dc.description.abstractBackground: The hemagglutinin (HA) glycoprotein is the principal target of protective humoral immune responses to influenza virus infections but such antibody responses only provide efficient protection against a narrow spectrum of HA antigenic variants within a given virus subtype. Avian influenza viruses such as H5N1 are currently panzootic and pose a pandemic threat. These viruses are antigenically diverse and protective strategies need to cross protect against diverse viral clades. Furthermore, there are 16 different HA subtypes and no certainty the next pandemic will be caused by an H5 subtype, thus it is important to develop prophylactic and therapeutic interventions that provide heterosubtypic protection. Methods and Findings: Here we describe a panel of 13 monoclonal antibodies (mAbs) recovered from combinatorial display libraries that were constructed from human IgM + memory B cells of recent (seasonal) influenza vaccinees. The mAbs have broad heterosubtypic neutralizing activity against antigenically diverse H1, H2, H5, H6, H8 and H9 influenza subtypes. Restriction to variable heavy chain gene IGHV1-69 in the high affinity mAb panel was associated with binding to a conserved hydrophobic pocket in the stem domain of HA. The most potent antibody (CR6261) was protective in mice when given before and after lethal H5N1 or H1N1 challenge. Conclusions: The human monoclonal CR6261 described in this study could be developed for use as a broad spectrum agent for prophylaxis or treatment of human or avian influenza infections without prior strain characterization. Moreover, the CR6261 epitope could be applied in targeted vaccine strategies or in the design of novel antivirals. Finally our approach of screening the IgM + memory repertoire could be applied to identify conserved and functionally relevant targets on other rapidly evolving pathogens. © 2008 Throsby et al.en_HK
dc.languageengen_HK
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAntibodies, Monoclonal - chemistry - immunology - isolation and purification-
dc.subject.meshB-Lymphocytes - immunology - virology-
dc.subject.meshImmunoglobulin M - immunology-
dc.subject.meshImmunologic Memory - immunology-
dc.subject.meshInfluenza A Virus, H1N1 Subtype - immunology-
dc.titleHeterosubtypic neutralizing monoclonal antibodies cross-protective against H5N1 and H1N1 recovered from human IgM + memory B cellsen_HK
dc.typeArticleen_HK
dc.identifier.emailPoon, LLM: llmpoon@hkucc.hku.hken_HK
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_HK
dc.identifier.emailPeiris, M: malik@hkucc.hku.hken_HK
dc.identifier.authorityPoon, LLM=rp00484en_HK
dc.identifier.authorityGuan, Y=rp00397en_HK
dc.identifier.authorityPeiris, M=rp00410en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0003942en_HK
dc.identifier.pmid19079604-
dc.identifier.pmcidPMC2596486-
dc.identifier.scopuseid_2-s2.0-58049198443en_HK
dc.identifier.hkuros164358en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-58049198443&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume3en_HK
dc.identifier.issue12en_HK
dc.identifier.spagee3942-
dc.identifier.epagee3942-
dc.identifier.isiWOS:000265458400003-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10001164711-
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza-
dc.identifier.scopusauthoridThrosby, M=26638530800en_HK
dc.identifier.scopusauthoridvan den Brink, E=6602122667en_HK
dc.identifier.scopusauthoridJongeneelen, M=8609959300en_HK
dc.identifier.scopusauthoridPoon, LLM=7005441747en_HK
dc.identifier.scopusauthoridAlard, P=36936435300en_HK
dc.identifier.scopusauthoridCornelissen, L=6506562393en_HK
dc.identifier.scopusauthoridBakker, A=7201772292en_HK
dc.identifier.scopusauthoridCox, F=8679913700en_HK
dc.identifier.scopusauthoridvan Deventer, E=8679914200en_HK
dc.identifier.scopusauthoridGuan, Y=7202924055en_HK
dc.identifier.scopusauthoridCinatl, J=35247582600en_HK
dc.identifier.scopusauthoridter Meulen, J=7006803276en_HK
dc.identifier.scopusauthoridLasters, I=7003749975en_HK
dc.identifier.scopusauthoridCarsetti, R=6701799426en_HK
dc.identifier.scopusauthoridPeiris, M=7005486823en_HK
dc.identifier.scopusauthoridde Kruif, J=6604049538en_HK
dc.identifier.scopusauthoridGoudsmit, J=35374719700en_HK
dc.identifier.citeulike6243940-

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