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-beta,
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.