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Text
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URL Address
<a href="http://doi.org/10.1016/j.vaccine.2003.11.062" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.vaccine.2003.11.062</a>
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Pages
2368-2373
Issue
19
Volume
22
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Title
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CEL-1000 - a peptide with adjuvant activity or Th1 immune responses
Publisher
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Vaccine
Date
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2004
2004-06
Subject
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Research & Experimental Medicine; Immunology; cytokines; antibodies; beta-2-microglobulin; vaccines; dna; antigens; CEL-1000; epitope; gamma interferon; IgG2a antibodies; liposomes
Creator
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Charoenvit Y; Goel N; Whelan M; Rosenthal K S; Zimmerman D H
Description
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CEL-1000 (derG, DGQEEKAGVVSTGLIGGG) is a small immunomodulatory peptide which delivers demonstrated protective activity in two infectious disease challenge models (HSV and malaria) and an allogenic tumor vaccine model. CEL-1000 and other activators (defensin-beta, CpG ODN, and imiquimod) of the innate immune system promote IFN-gamma-associated protective responses. CEL-1000 is an improved form of peptide G (a peptide from human MHC II beta chain second domain, aa 135-149) known to enhance immune responses of other immunogenic peptides. Since defensin-P, CpG ODN, and imiquimod have been shown to possess adjuvant activity, we investigated the adjuvant effect of peptide G and CEL-1000 as conjugates with HIV and malaria peptides. Antibody titers and isotypes were evaluated on serum taken from select days following immunization. Results for CEL-1000 and G peptide conjugates were compared with results for KLH conjugates of the same HIV peptide from the p 17 molecule (87-116) referred to as HGP-30. Studies demonstrated that comparable titers were seen on day 28, 42, 63, and 77 with either G or KLH-HGP-30 peptide conjugates. In another study, CEL-1000 conjugates (CEL-1000-HGP-30) demonstrated a 4-10-fold higher titer antibody response than seen with several other peptide conjugates of the same HGP-30 peptide. Improved adjuvant activity of CEL-1000 in peptide conjugates was also demonstrated by a shift in the antibody isotypes toward a Th1 response (IgG2a). The IgG2a/IgG1, ratio for G-HGP-30 HIV or KLH-HGP-30 HIV conjugates were lower than for the CEL-1000-HGP-30 HIV conjugate. A similar favoring of the IgG2a/IgG1 ratio was seen for a malaria peptide conjugate (CEL-1000-SF/GF) compared to the un-conjugated peptide (SF-GF). CEL-1000 also showed adjuvant activity in an allogenic tumor vaccine model. As expected for an adjuvant, CEL-1000 or G does not induce detectable self-directed or cross reactive antibodies. CEL-1000 is currently being investigated for use as an adjuvant with conventional vaccines. It is expected that IgG2a antibodies would be preferably generated by CEL-1000 adjuvancy and could enhance in vivo clearance of antigens or pathogens. (C) 2004 Elsevier Ltd. All rights reserved.
Identifier
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<a href="http://doi.org/10.1016/j.vaccine.2003.11.062" target="_blank" rel="noreferrer noopener">10.1016/j.vaccine.2003.11.062</a>
Format
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Journal Article or Conference Abstract Publication
2004
Antibodies
Antigens
beta-2-microglobulin
CEL-1000
Charoenvit Y
Cytokines
DNA
epitope
gamma interferon
Goel N
IgG2a antibodies
Immunology
Journal Article or Conference Abstract Publication
liposomes
Research & Experimental Medicine
Rosenthal K S
Vaccine
Vaccines
Whelan M
Zimmerman D H