Comparative immunogenicity of HIV-1 clade C envelope proteins for prime/boost studies.
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 articleSubject
AnimalsAntibody Formation
Antigens, CD4
Cell Line
Guinea Pigs
HIV Envelope Protein gp120
HIV-1
Immune Sera
Immunization, Secondary
Neutralization Tests
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https://hdl.handle.net/10161/4560Published Version (Please cite this version)
10.1371/journal.pone.0012076Publication Info
Smith, Douglas H; Winters-Digiacinto, Peggy; Mitiku, Misrach; O'Rourke, Sara; Sinangil,
Faruk; Wrin, Terri; ... Berman, Phillip W (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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Show full item recordScholars@Duke
David Charles Montefiori
Professor in Surgery
Dr. Montefiori is Professor and Director of the Laboratory for HIV and COVID-19 Vaccine
Research & Development in the Department of Surgery, Division of Surgical Sciences
at Duke University Medical Center. His major research interests are viral immunology
and HIV and COVID-19 vaccine development, with a special emphasis on neutralizing
antibodies. Multiple aspects of HIV-1 neutralizing antibodies are studied in his laboratory,
including mechanisms of neutralization and escape,

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