TY - JOUR
T1 - CEL-1000 - A peptide with adjuvant activity for Th1 immune responses
AU - Charoenvit, Yupin
AU - Goel, Neena
AU - Whelan, Michael
AU - Rosenthal, Kenneth S.
AU - Zimmerman, Daniel H.
N1 - Funding Information:
The opinions and assertions herein are the private ones of the authors and are not to be construed as official or as reflecting the views of the US Navy or the department of Defense. Part of this work was supported by a fund allocated to the Naval Medical Research Center, work unit number 6000.RAD1.F.A0309; and a fund from CEL-SCI Corporation, NCRADA NMRC-96-NMR-500. The experiments reported herein were conducted according to the principles set forth in the “Guide for the Care and Use of laboratory Animals.” Institute of Laboratory Animal Resources, National Research Council, National Academy Press, 1966.
PY - 2004/6/23
Y1 - 2004/6/23
N2 - 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.
AB - 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.
KW - CEL-1000
KW - Cytokines
KW - Gamma interferon
KW - IgG2a antibodies
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UR - http://www.scopus.com/inward/citedby.url?scp=2942534189&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2003.11.062
DO - 10.1016/j.vaccine.2003.11.062
M3 - Article
C2 - 15193396
AN - SCOPUS:2942534189
SN - 0264-410X
VL - 22
SP - 2368
EP - 2373
JO - Vaccine
JF - Vaccine
IS - 19
ER -
