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CEL-1000 - a peptide with adjuvant activity or Th1 immune responses

机译：CEL-1000-具有佐剂活性或Th1免疫应答的肽

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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.
机译：CEL-1000（derG，DGQEEKAGVVSTGLIGGG）是一种小型免疫调节肽，在两种传染病攻击模型（HSV和疟疾）和同种异体肿瘤疫苗模型中均具有已证明的保护活性。先天性免疫系统的CEL-1000和其他激活剂（防御素β，CpG ODN和咪喹莫特）促进IFN-γ相关的保护反应。 CEL-1000是肽G（来自人MHC IIβ链第二结构域的肽，氨基酸135-149）的改良形式，已知可增强其他免疫原性肽的免疫应答。由于防御素-P，CpG ODN和咪喹莫特已显示具有佐剂活性，因此我们研究了肽G和CEL-1000与HIV和疟疾肽的结合物的佐剂作用。在免疫后选定天数的血清上评估抗体滴度和同种型。将CEL-1000和G肽偶联物的结果与相同HIV肽的p17分子（87-116）称为HGP-30的KLH偶联物的结果进行了比较。研究表明，在第28、42、63和77天使用G或KLH-HGP-30肽偶联物可观察到相似的滴度。在另一项研究中，与相同HGP-30肽的其他几种肽缀合物相比，CEL-1000缀合物（CEL-1000-HGP-30）的效价抗体反应高4-10倍。抗体同种型向Th1应答（IgG2a）的转变也证明了CEL-1000在肽偶联物中的佐剂活性得到改善。 G-HGP-30 HIV或KLH-HGP-30 HIV缀合物的IgG2a / IgG1比低于CEL-1000-HGP-30 HIV缀合物。与非缀合肽（SF-GF）相比，疟疾肽缀合物（CEL-1000-SF / GF）的IgG2a / IgG1比率具有相似的优势。 CEL-1000在同种异体肿瘤疫苗模型中也显示出佐剂活性。如佐剂所预期的，CEL-1000或G不会诱导可检测的自指导或交叉反应抗体。目前正在研究将CEL-1000用作常规疫苗的佐剂。预期IgG2a抗体将优选通过CEL-1000佐剂产生，并可以增强抗原或病原体的体内清除率。

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