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.
Publication types
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Clinical Trial
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Controlled Clinical Trial
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Randomized Controlled Trial
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylmuramyl-Alanyl-Isoglutamine / administration & dosage
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Acetylmuramyl-Alanyl-Isoglutamine / adverse effects
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Acetylmuramyl-Alanyl-Isoglutamine / analogs & derivatives*
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Acetylmuramyl-Alanyl-Isoglutamine / immunology
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Adjuvants, Immunologic* / administration & dosage
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Adjuvants, Immunologic* / adverse effects
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Adult
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Animals
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Antibodies, Viral / biosynthesis*
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Dizziness / etiology
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Emulsions / administration & dosage
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Emulsions / adverse effects
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Endotoxins / adverse effects
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Endotoxins / analysis
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Erythema / etiology
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Fatigue / etiology
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Fever / chemically induced
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Humans
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Influenza A virus / immunology*
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Influenza B virus / immunology*
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Influenza Vaccines* / administration & dosage
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Influenza Vaccines* / adverse effects
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Influenza Vaccines* / immunology
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Injections, Intramuscular
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Male
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Nausea / etiology
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Neutralization Tests
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Pain / etiology
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Phosphatidylethanolamines* / administration & dosage
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Phosphatidylethanolamines* / adverse effects
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Phosphatidylethanolamines* / immunology
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Pilot Projects
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Rabbits
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Safety
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Vaccines, Inactivated / administration & dosage
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Vaccines, Inactivated / adverse effects
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Vaccines, Inactivated / immunology
Substances
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Adjuvants, Immunologic
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Antibodies, Viral
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Emulsions
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Endotoxins
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Influenza Vaccines
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Phosphatidylethanolamines
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Vaccines, Inactivated
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mifamurtide
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Acetylmuramyl-Alanyl-Isoglutamine