Publication

Safety and tolerability evaluation of the use of Montanide ISA™51 as vaccine adjuvant: A systematic review

van Doorn, E., Liu, H., Huckriede, A. & Hak, E., Jan-2016, In : Human vaccines & immunotherapeutics. 12, 1, p. 159-169 11 p.

Research output: Contribution to journalReview articleAcademicpeer-review

Montanide ISA (TM) 51 (ISA 51) is a vaccine adjuvant which has been tested in therapeutic and prophylactic vaccine trials. The aim of this review is to present a comprehensive examination of the safety and tolerability of ISA 51 containing vaccines. A systematic literature search was conducted in PubMed, EMBASE and clinicaltrials.gov. Eligible studies were categorized into: (A) uncontrolled studies with non-healthy subjects, (B) controlled studies with non-healthy subjects, and (C) controlled studies with healthy subjects. Reported adverse events (AEs) were assessed. 91 studies were included in our review. Generally observed AEs included injection site reaction; injection site pain; myalgia; headache; gastro-intestinal disorders; fatigue and fever - regardless of the administration route and subject characteristic. Specific AEs, e.g. injection site reactions and rash, were more frequently reported from subjects receiving ISA 51-adjuvanted vaccines than from subjects receiving antigen or ISA 51 only. The reported AEs were mainly mild to moderate in intensity. Serious AEs (SAEs) were reported in 27% of the uncontrolled trials and 2 trials conducted with healthy subjects. Notably, 2 other trials conducted with healthy subjects were stopped due to unacceptable AEs. Some studies indicate that the mixing procedure of antigen and adjuvant might influence the occurrence of AEs. Reports on SAEs and premature termination of 2 trials advise caution when using ISA 51. Yet, AEs might be preventable by proper mixing of vaccine and adjuvant to a stable emulsion. Trials including an active control group are needed for a fair evaluation of adjuvant safety.

Original languageEnglish
Pages (from-to)159-169
Number of pages11
JournalHuman vaccines & immunotherapeutics
Volume12
Issue number1
Early online date17-Sep-2015
Publication statusPublished - Jan-2016

    Keywords

  • adverse event, ISA 51, Montanide, safety, systematic review, tolerability, PEPTIDE-BASED IMMUNOTHERAPY, TRANSMISSION-BLOCKING VACCINE, INCOMPLETE FREUNDS-ADJUVANT, T-CELL RESPONSES, PHASE-I TRIAL, CANCER VACCINE, MELANOMA PATIENTS, COMPLETE REMISSION, BREAST-CANCER, DOUBLE-BLIND

ID: 23819463