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Article: Putative rhesus macaque germline predecessors of human broadly HIV-neutralizing antibodies: Differences from the human counterparts and implications for HIV-1 vaccine development

TitlePutative rhesus macaque germline predecessors of human broadly HIV-neutralizing antibodies: Differences from the human counterparts and implications for HIV-1 vaccine development
Authors
KeywordsB-cell repertoire
HIV/AIDS
Neutralizing antibodies
Rhesus macaque
Somatic maturation
Vaccine
Issue Date2011
PublisherElsevier Ltd. The Journal's web site is located at http://www.elsevier.com/locate/vaccine
Citation
Vaccine, 2011, v. 29 n. 40, p. 6903-6910 How to Cite?
AbstractBroadly neutralizing antibodies (bnAbs) are likely to be a key component of protective immunity conferred by an effective HIV-1 vaccine. We and others have reported that putative human germline predecessors of known human bnAbs lack measurable binding to HIV-1 envelope glycoproteins (Env), which could be a new challenge for eliciting human bnAbs. Rhesus macaques have been used as nonhuman primate models for testing vaccine candidates, but little is known about their germline Abs. Here we show the similarities and differences between putative rhesus macaque and human germline predecessors and possible intermediate antibodies of one of the best characterized bnAbs, b12. Similar to the human counterpart, a putative rhesus macaque b12 germline antibody lacks measurable binding to HIV-1 Envs, suggesting that initiation of somatic maturation of rhesus macaque germline b12 predecessor may also be a challenge. However, differences in sequence characteristics and binding properties between macaque and human b12 germline and intermediate antibodies suggest that the two germline predecessors may undergo different maturation pathways in rhesus macaques and in humans. These results indicate that immunogens that could initiate the immune responses and drive somatic mutations leading to elicitation of b12 or b12-like bnAbs in rhesus macaques and in humans are likely to be different. This has important implications for HIV-1 vaccine development. © 2011 Elsevier Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/135267
ISSN
2015 Impact Factor: 3.413
2015 SCImago Journal Rankings: 2.044
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong
General Research Fund (GRF) of Hong Kong
CCR, NCI, NIH
Bill and Melinda Gates Foundation
Funding Information:

We thank Jeffrey Lifson, Nancy Longo, Ruth Ruprecht, Peter Kwong, Tongqing Zhou, Xiaodong Xiao, Prabakaran Ponraj and Zhiwei Chen for helpful discussions, Jeffrey Lifson for providing rhesus macaque PBMCs, Gerald Quinnan and Dennis Burton for providing reagents. This work was supported by the Intramural Research Program of the University of Hong Kong, and by the General Research Fund (GRF) of Hong Kong to M-Y.Z., and by the Intramural Research Program of the CCR, NCI, NIH, and the Bill and Melinda Gates Foundation to D.S.D.

References

 

DC FieldValueLanguage
dc.contributor.authorYuan, Ten_HK
dc.contributor.authorLi, Jen_HK
dc.contributor.authorZhang, Yen_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorStreaker, Een_HK
dc.contributor.authorDimitrov, DSen_HK
dc.contributor.authorZhang, MYen_HK
dc.date.accessioned2011-07-27T01:30:54Z-
dc.date.available2011-07-27T01:30:54Z-
dc.date.issued2011en_HK
dc.identifier.citationVaccine, 2011, v. 29 n. 40, p. 6903-6910en_HK
dc.identifier.issn0264-410Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/135267-
dc.description.abstractBroadly neutralizing antibodies (bnAbs) are likely to be a key component of protective immunity conferred by an effective HIV-1 vaccine. We and others have reported that putative human germline predecessors of known human bnAbs lack measurable binding to HIV-1 envelope glycoproteins (Env), which could be a new challenge for eliciting human bnAbs. Rhesus macaques have been used as nonhuman primate models for testing vaccine candidates, but little is known about their germline Abs. Here we show the similarities and differences between putative rhesus macaque and human germline predecessors and possible intermediate antibodies of one of the best characterized bnAbs, b12. Similar to the human counterpart, a putative rhesus macaque b12 germline antibody lacks measurable binding to HIV-1 Envs, suggesting that initiation of somatic maturation of rhesus macaque germline b12 predecessor may also be a challenge. However, differences in sequence characteristics and binding properties between macaque and human b12 germline and intermediate antibodies suggest that the two germline predecessors may undergo different maturation pathways in rhesus macaques and in humans. These results indicate that immunogens that could initiate the immune responses and drive somatic mutations leading to elicitation of b12 or b12-like bnAbs in rhesus macaques and in humans are likely to be different. This has important implications for HIV-1 vaccine development. © 2011 Elsevier Ltd.en_HK
dc.languageengen_US
dc.publisherElsevier Ltd. The Journal's web site is located at http://www.elsevier.com/locate/vaccineen_HK
dc.relation.ispartofVaccineen_HK
dc.subjectB-cell repertoireen_HK
dc.subjectHIV/AIDSen_HK
dc.subjectNeutralizing antibodiesen_HK
dc.subjectRhesus macaqueen_HK
dc.subjectSomatic maturationen_HK
dc.subjectVaccineen_HK
dc.titlePutative rhesus macaque germline predecessors of human broadly HIV-neutralizing antibodies: Differences from the human counterparts and implications for HIV-1 vaccine developmenten_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0264-410X&volume=29&issue=40&spage=6903&epage=6910&date=2011&atitle=Putative+rhesus+macaque+germline+predecessors+of+human+broadly+HIV-neutralizing+antibodies:+differences+from+the+human+counterparts+and+implications+for+HIV-1+vaccine+development-
dc.identifier.emailZhang, MY:zhangmy@hku.hken_HK
dc.identifier.authorityZhang, MY=rp01409en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.vaccine.2011.07.046en_HK
dc.identifier.pmid21807049-
dc.identifier.pmcidPMC3167946-
dc.identifier.scopuseid_2-s2.0-80052314665en_HK
dc.identifier.hkuros188244en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80052314665&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume29en_HK
dc.identifier.issue40en_HK
dc.identifier.spage6903en_HK
dc.identifier.epage6910en_HK
dc.identifier.eissn1873-2518-
dc.identifier.isiWOS:000295300500012-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridYuan, T=44161519800en_HK
dc.identifier.scopusauthoridLi, J=51261181100en_HK
dc.identifier.scopusauthoridZhang, Y=51261659200en_HK
dc.identifier.scopusauthoridWang, Y=49662536300en_HK
dc.identifier.scopusauthoridStreaker, E=36944557300en_HK
dc.identifier.scopusauthoridDimitrov, DS=7202564539en_HK
dc.identifier.scopusauthoridZhang, MY=35316639300en_HK
dc.identifier.citeulike9625240-

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