CEL-1000 - A peptide with adjuvant activity for Th1 immune responses

Yupin Charoenvit, Neena Goel, Michael Whelan, Kenneth S. Rosenthal, Daniel H. Zimmerman

Research output: Contribution to journalArticle

Abstract

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-β, CpG ODN, and imiquimod) of the innate immune system promote IFN-γ-associated protective responses. CEL-1000 is an improved form of peptide G (a peptide from human MHC II β chain second domain, aa 135-149) known to enhance immune responses of other immunogenic peptides. Since defensin-β, 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 p17 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.

Original languageEnglish (US)
Pages (from-to)2368-2373
Number of pages6
JournalVaccine
Volume22
Issue number19
DOIs
StatePublished - Jun 23 2004
Externally publishedYes

Fingerprint

adjuvants
immune response
peptides
Peptides
imiquimod
HIV
antibodies
Malaria
Defensins
malaria
Cancer Vaccines
Antibodies
vaccines
Immunoglobulin G
neoplasms
disease models
Antibody Formation
Communicable Diseases
infectious diseases
Immune System

Keywords

  • CEL-1000
  • Cytokines
  • Gamma interferon
  • IgG2a antibodies

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Charoenvit, Y., Goel, N., Whelan, M., Rosenthal, K. S., & Zimmerman, D. H. (2004). CEL-1000 - A peptide with adjuvant activity for Th1 immune responses. Vaccine, 22(19), 2368-2373. https://doi.org/10.1016/j.vaccine.2003.11.062

CEL-1000 - A peptide with adjuvant activity for Th1 immune responses. / Charoenvit, Yupin; Goel, Neena; Whelan, Michael; Rosenthal, Kenneth S.; Zimmerman, Daniel H.

In: Vaccine, Vol. 22, No. 19, 23.06.2004, p. 2368-2373.

Research output: Contribution to journalArticle

Charoenvit, Y, Goel, N, Whelan, M, Rosenthal, KS & Zimmerman, DH 2004, 'CEL-1000 - A peptide with adjuvant activity for Th1 immune responses', Vaccine, vol. 22, no. 19, pp. 2368-2373. https://doi.org/10.1016/j.vaccine.2003.11.062
Charoenvit Y, Goel N, Whelan M, Rosenthal KS, Zimmerman DH. CEL-1000 - A peptide with adjuvant activity for Th1 immune responses. Vaccine. 2004 Jun 23;22(19):2368-2373. https://doi.org/10.1016/j.vaccine.2003.11.062
Charoenvit, Yupin ; Goel, Neena ; Whelan, Michael ; Rosenthal, Kenneth S. ; Zimmerman, Daniel H. / CEL-1000 - A peptide with adjuvant activity for Th1 immune responses. In: Vaccine. 2004 ; Vol. 22, No. 19. pp. 2368-2373.
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