title: Pilot evaluation of influenza virus vaccine (IVV) combined with adjuvant.
abstract: The safety of licensed influenza virus vaccine (IVV) combined with a novel adjuvant containing muramyl tripeptide (MTP) conjugated to phosphatidylethanolamine (PE) was evaluated in a randomized pilot study. Ten healthy 23-30-year-old men were given a single intramuscular dose of IVV combined with saline (n = 5) or with 100 micrograms of MTP-PE in the MF59 adjuvant emulsion (MF59-100) (n = 5). Evaluations were performed on days 0, 1, 2, 4, 7 and 28 after inoculation. IVV alone was well tolerated. All volunteers immunized with IVV/MF59-100 experienced moderate to severe local and systemic reactions which interfered with usual activities. Discomfort at the injection site was first noted at 2-6 h; induration (5/5), erythema (3/5), and regional adenopathy (3/5) persisted for up to 4 days. Systemic symptoms including chills (5/5), fever (3/5), nausea (3/5) and/or dizziness (2/5) developed within 12 h of inoculation and resolved by 48 h. Elevated white blood cell count (days 1 and 2), erythrocyte sedimentation rate and serum fibrinogen were transiently observed. Although peak serum neutralizing antibody titres versus influenza A/H3N2 and influenza B antigens were higher in the group given IVV with MF59-100, these unexpected reactions indicate that this dose of adjuvant is unsuitable for use in combination with this IVV.
authors.affiliation: Baylor College of Medicine, Department of Microbiology and Immunology, Houston, TX 77030.
authors.forename: W
authors.initials: W
authors.lastname: Keitel
authors.forename: R
authors.initials: R
authors.lastname: Couch
authors.forename: N
authors.initials: N
authors.lastname: Bond
authors.forename: S
authors.initials: S
authors.lastname: Adair
authors.forename: G
authors.initials: G
authors.lastname: Van Nest
authors.forename: C
authors.initials: C
authors.lastname: Dekker
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D004244:Dizziness / Q000209:etiology; D004655:Emulsions / Q000008:administration & dosage / Q000009:adverse effects; D004731:Endotoxins / Q000009:adverse effects / Q000032:analysis; D004890:Erythema / Q000209:etiology; D005221:Fatigue / Q000209:etiology; D005334:Fever / Q000139:chemically induced; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D009981:Influenza B virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D007273:Injections, Intramuscular; D008297:Male; D009325:Nausea / Q000209:etiology; D009500:Neutralization Tests; D010146:Pain / Q000209:etiology; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D010865:Pilot Projects; D011817:Rabbits; D012449:Safety; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004655:Emulsions; D004731:Endotoxins; D007252:Influenza Vaccines; D010714:Phosphatidylethanolamines; D015164:Vaccines, Inactivated; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine