Abstract
Adjuvants are requisite components of many vaccines designed to elicit T-cell immunity although the exact components of commonly used adjuvants are not always fully defined. In 2006, owing to concerns of prion contamination, the formulation of Montanide ISA 51 Incomplete Freund's Adjuvant (IFA) was changed from using oleic acid isolated from beef tallow to that isolated from olives. In sequential clinical trials in the Surgery Branch, NCI patients at high risk for recurrence of melanoma were immunized with the gp100 melanoma/melanocyte antigenic peptide, gp100: 209-217 (210M), emulsified in the beef-derived IFA or the olive-derived IFA. The in vivo generation of gp100 reactive T cells was significantly less in patients receiving the olive compared with the beef IFA as assessed by both ELISPOT (P2=0.0001) and in vitro sensitization assays (P2=0.0001). Local skin reactions to the peptide emulsion were also far less severe using the olive IFA (P2=0.0003). Thus it seems likely that contaminants in the beef-derived IFA played an important role in the increased adjuvanticity of this preparation compared with the olive-derived IFA. These findings raise serious concerns related to the use of the available olive-derived IFA for immunization in clinical trials. A survey of ongoing clinical trials listed in ClinicalTrials.gov revealed 36 trials currently accruing patients that are using the olive-derived Montanide ISA 51 IFA.