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Article: Cross-reactive HIV-1-neutralizing activity of serum IgG from a rabbit immunized with gp41 fused to IgG1 Fc: Possible role of the prolonged half-life of the immunogen

TitleCross-reactive HIV-1-neutralizing activity of serum IgG from a rabbit immunized with gp41 fused to IgG1 Fc: Possible role of the prolonged half-life of the immunogen
Authors
Issue Date2009
PublisherElsevier Ltd. The Journal's web site is located at http://www.elsevier.com/locate/vaccine
Citation
Vaccine, 2009, v. 27 n. 6, p. 857-863 How to Cite?
AbstractThe elicitation of broadly cross-reactive HIV-1 neutralizing antibodies in humans remains a major challenge in developing a viable AIDS vaccine. We hypothesized that prolonged exposure to candidate vaccine immunogens could enhance the elicitation of such antibodies. In an attempt to develop HIV-1 vaccine immunogens with prolonged half-lives and increased stability, we constructed a fusion protein, gp41Fc, in which a truncated HIV-1 gp4189.6 was fused to a human IgG1 Fc. Gp41Fc is stable in solution, retains its antigenic structure and is highly immunogenic in rabbits. The serum titers reached 1:102,400 for the gp41Fc and 1:5,120 for gp14089.6. Rabbit IgG neutralized diverse HIV-1 isolates and HIV-2, and the neutralization activity was attributed to gp41-specific IgG. The concentration of the gp41Fc in the serum correlated with the neutralization activity of rabbit IgG which recognized mostly conformation-independent epitopes on gp41 and predominantly bound to peptides derived from the gp41 immunodominant loop region. These results suggest that the prolonged half-life of gp41Fc in the serum may enhance the generation of cross-reactive neutralizing antibodies. Further research is needed to confirm and extend these results which may have implications for the development of vaccine immunogens with enhanced capability to elicit cross-reactive HIV-1-neutralizing antibodies. © 2008 Elsevier Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/157537
ISSN
2015 Impact Factor: 3.413
2015 SCImago Journal Rankings: 2.044
ISI Accession Number ID
Funding AgencyGrant Number
NIH
National Cancer InstituteN01-CO-12400
Center for Cancer Research
Gates Foundation
Southern Research Institute
Funding Information:

We thank Dr. Shibo Jiang for providing mouse mAb NC-1 and Dr. Christopher Broder for mouse mAbs T3 and D61. We also thank Drs. Shibo Jiang and Xiaodong Xiao for helpful discussions, Vidita Choudhry for help with pseudovirus assay and John Owens for help with manuscript preparation. We thank one of the reviewers for Suggesting to explore gp140Fc fusion proteins as vaccine irnmunogens. This research was supported by the NIH Intramural AIDS Targeted Antiviral Program (IATAP), the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and the Gates Foundation to DSD, and by internal funds from Southern Research Institute. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

References

 

DC FieldValueLanguage
dc.contributor.authorZhang, MYen_US
dc.contributor.authorWang, Yen_US
dc.contributor.authorMankowski, MKen_US
dc.contributor.authorPtak, RGen_US
dc.contributor.authorDimitrov, DSen_US
dc.date.accessioned2012-08-08T08:51:03Z-
dc.date.available2012-08-08T08:51:03Z-
dc.date.issued2009en_US
dc.identifier.citationVaccine, 2009, v. 27 n. 6, p. 857-863en_US
dc.identifier.issn0264-410Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/157537-
dc.description.abstractThe elicitation of broadly cross-reactive HIV-1 neutralizing antibodies in humans remains a major challenge in developing a viable AIDS vaccine. We hypothesized that prolonged exposure to candidate vaccine immunogens could enhance the elicitation of such antibodies. In an attempt to develop HIV-1 vaccine immunogens with prolonged half-lives and increased stability, we constructed a fusion protein, gp41Fc, in which a truncated HIV-1 gp4189.6 was fused to a human IgG1 Fc. Gp41Fc is stable in solution, retains its antigenic structure and is highly immunogenic in rabbits. The serum titers reached 1:102,400 for the gp41Fc and 1:5,120 for gp14089.6. Rabbit IgG neutralized diverse HIV-1 isolates and HIV-2, and the neutralization activity was attributed to gp41-specific IgG. The concentration of the gp41Fc in the serum correlated with the neutralization activity of rabbit IgG which recognized mostly conformation-independent epitopes on gp41 and predominantly bound to peptides derived from the gp41 immunodominant loop region. These results suggest that the prolonged half-life of gp41Fc in the serum may enhance the generation of cross-reactive neutralizing antibodies. Further research is needed to confirm and extend these results which may have implications for the development of vaccine immunogens with enhanced capability to elicit cross-reactive HIV-1-neutralizing antibodies. © 2008 Elsevier Ltd.en_US
dc.languageengen_US
dc.publisherElsevier Ltd. The Journal's web site is located at http://www.elsevier.com/locate/vaccineen_US
dc.relation.ispartofVaccineen_US
dc.subject.meshAids Vaccines - Genetics - Immunology - Pharmacokineticsen_US
dc.subject.meshAdjuvants, Immunologic - Genetics - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshFemaleen_US
dc.subject.meshHiv Antibodies - Blooden_US
dc.subject.meshHiv Envelope Protein Gp41 - Genetics - Immunologyen_US
dc.subject.meshHiv-1 - Genetics - Immunologyen_US
dc.subject.meshHiv-2 - Immunologyen_US
dc.subject.meshHalf-Lifeen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunoglobulin Fc Fragments - Genetics - Pharmacologyen_US
dc.subject.meshNeutralization Testsen_US
dc.subject.meshRabbitsen_US
dc.subject.meshRecombinant Fusion Proteins - Genetics - Immunology - Pharmacokineticsen_US
dc.titleCross-reactive HIV-1-neutralizing activity of serum IgG from a rabbit immunized with gp41 fused to IgG1 Fc: Possible role of the prolonged half-life of the immunogenen_US
dc.typeArticleen_US
dc.identifier.emailZhang, MY:zhangmy@hku.hken_US
dc.identifier.authorityZhang, MY=rp01409en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.vaccine.2008.11.083en_US
dc.identifier.pmid19084043-
dc.identifier.scopuseid_2-s2.0-58249100316en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-58249100316&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume27en_US
dc.identifier.issue6en_US
dc.identifier.spage857en_US
dc.identifier.epage863en_US
dc.identifier.isiWOS:000263421800008-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridZhang, MY=35316639300en_US
dc.identifier.scopusauthoridWang, Y=7601512395en_US
dc.identifier.scopusauthoridMankowski, MK=12142254400en_US
dc.identifier.scopusauthoridPtak, RG=7004558299en_US
dc.identifier.scopusauthoridDimitrov, DS=7202564539en_US

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