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Hepatitis C virus soluble E2 in combination with QuilA and CpG ODN induces neutralizing antibodies in mice.

Abstract
Several studies have emphasized the importance of an early, highly neutralizing antibody response in the clearance of Hepatitis C virus (HCV) infection. The envelope glycoprotein E2 is a major target for HCV neutralizing antibodies. Here, we compared antibody responses in mice immunized with native soluble E2 (sE2) from the H77 1a isolate coupled with different adjuvants or combinations of adjuvants. Adjuvanting sE2 with Freund's, monophosphoryl lipid A (MPL), cytosine phosphorothioate guanine oligodeoxynucleotide (CpG ODN), or alpha-galactosylceramide (αGalCer) derivatives elicited only moderate antibody responses. In contrast, immunizations with sE2 and QuilA elicited exceptionally high anti-E2 antibody titers. Sera from these mice effectively neutralized HCV pseudoparticles (HCVpp) 1a entry. Moreover, the combination of QuilA and CpG ODN further enhanced neutralizing antibody titers wherein cross-neutralization of HCVpp 4 was observed. We conclude that the combination of QuilA and CpG ODN is a promising adjuvant combination that should be further explored for the development of an HCV subunit vaccine. Our work also emphasizes that the ideal combination of adjuvant and immunogen has to be determined empirically.
AuthorsMarloes A Naarding, Emilia Falkowska, Hui Xiao, Tatjana Dragic
JournalVaccine (Vaccine) Vol. 29 Issue 16 Pg. 2910-7 (Apr 05 2011) ISSN: 1873-2518 [Electronic] Netherlands
PMID21338680 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Ltd. All rights reserved.
Chemical References
  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • CpG ODN 1826
  • Galactosylceramides
  • Hepatitis C Antibodies
  • Oligodeoxyribonucleotides
  • Quillaja Saponins
  • Saponins
  • Viral Envelope Proteins
  • Viral Hepatitis Vaccines
  • alpha-galactosylceramide
  • glycoprotein E2, Hepatitis C virus
  • Quil A
  • KRN 7000
Topics
  • Adjuvants, Immunologic (pharmacology)
  • Animals
  • Antibodies, Neutralizing (blood)
  • Cell Line, Tumor
  • Female
  • Galactosylceramides (immunology)
  • Hepacivirus (immunology)
  • Hepatitis C Antibodies (blood)
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Oligodeoxyribonucleotides (immunology)
  • Quillaja Saponins
  • Saponins (immunology)
  • Viral Envelope Proteins (immunology)
  • Viral Hepatitis Vaccines (immunology)

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