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    Comparative immunogenicity of HIV-1 clade C envelope proteins for prime/boost studies.

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    Date
    2010-08-11
    Authors
    Berman, PW
    Mitiku, M
    Montefiori, David Charles
    O'Rourke, S
    Sinangil, F
    Smith, DH
    Winters-Digiacinto, P
    Wrin, T
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    Abstract
    BACKGROUND: Previous clinical efficacy trials failed to support the continued development of recombinant gp120 (rgp120) as a candidate HIV vaccine. However, the recent RV144 HIV vaccine trial in Thailand showed that a prime/boost immunization strategy involving priming with canarypox vCP1521 followed by boosting with rgp120 could provide significant, although modest, protection from HIV infection. Based on these results, there is renewed interest in the development of rgp120 based antigens for follow up vaccine trials, where this immunization approach can be applied to other cohorts at high risk for HIV infection. Of particular interest are cohorts in Africa, India, and China that are infected with clade C viruses. METHODOLOGY/PRINCIPAL FINDINGS: A panel of 10 clade C rgp120 envelope proteins was expressed in 293 cells, purified by immunoaffinity chromatography, and used to immunize guinea pigs. The resulting sera were collected and analyzed in checkerboard experiments for rgp120 binding, V3 peptide binding, and CD4 blocking activity. Virus neutralization studies were carried out with two different assays and two different panels of clade C viruses. A high degree of cross reactivity against clade C and clade B viruses and viral proteins was observed. Most, but not all of the immunogens tested elicited antibodies that neutralized tier 1 clade B viruses, and some sera neutralized multiple clade C viruses. Immunization with rgp120 from the CN97001 strain of HIV appeared to elicit higher cross neutralizing antibody titers than the other antigens tested. CONCLUSIONS/SIGNIFICANCE: While all of the clade C antigens tested were immunogenic, some were more effective than others in eliciting virus neutralizing antibodies. Neutralization titers did not correlate with rgp120 binding, V3 peptide binding, or CD4 blocking activity. CN97001 rgp120 elicited the highest level of neutralizing antibodies, and should be considered for further HIV vaccine development studies.
    Type
    Journal article
    Subject
    Animals
    Antibody Formation
    Antigens, CD4
    Cell Line
    Guinea Pigs
    HIV Envelope Protein gp120
    HIV-1
    Immune Sera
    Immunization, Secondary
    Neutralization Tests
    Permalink
    https://hdl.handle.net/10161/4560
    Published Version (Please cite this version)
    10.1371/journal.pone.0012076
    Publication Info
    Berman, PW; Mitiku, M; Montefiori, David Charles; O'Rourke, S; Sinangil, F; Smith, DH; ... Wrin, T (2010). Comparative immunogenicity of HIV-1 clade C envelope proteins for prime/boost studies. PLoS One, 5(8). pp. e12076. 10.1371/journal.pone.0012076. Retrieved from https://hdl.handle.net/10161/4560.
    This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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    Scholars@Duke

    Montefiori

    David Charles Montefiori

    Professor of Surgery
    Dr. Montefiori is Professor and Director of the Laboratory for AIDS Vaccine Research and Development in the Department of Surgery, Division of Surgical Sciences, Duke University Medical Center. His major research interests are viral immunology and AIDS vaccine development, with a special emphasis on neutralizing antibodies. One of his highest priorities is to identify immunogens that generate broadly cross-reactive neutralizing antibodies for inclusion in HIV vaccines.  Many aspects of the
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