Abstract
As new vaccines are developed, novel adjuvants may play an important role in eliciting an effective immune response. We evaluated the safety and adjuvant properties of monophosphoryl lipid A (MPL in 129 healthy toddlers immunized with two doses of nine-valent pneumococcal-CRM(197) protein conjugate vaccine (PCV9) combined with 10, 25, or 50 micro g of MPL with or without alum (AlPO(4)). Vaccine-specific humoral and cell-mediated responses were examined following the second dose of study vaccine. All doses of MPL were well-tolerated and a dose-dependent effect of MPL on specific cellular responses was observed. The 10 micro g MPL dose significantly enhanced CRM(197)-specific T-cell proliferation (P=0.02) and interferon-gamma (INF-gamma) production (P=0.009) compared to responses of controls who received PCV9 with AlPO(4). In contrast, CRM(197)-specific T-cell proliferation and interferon-gamma production of the 50 micro g MPL/AlPO(4) group were decreased when compared to controls although these differences did not reach statistical significance. IL-5 and IL-13 responses after immunization showed a similar pattern with increased production in the 10 micro g MPL group and decreased production in the 50 micro g MPL/AlPO(4) group compared to controls. There were no differences in serum IgG antibody concentrations to the nine vaccine pneumococcal capsular polysaccharides and carrier protein between the MPL-containing and control vaccine groups. These findings demonstrate a dose-dependent effect of MPL on T-helper cell type 1 (TH-1) responses to the carrier protein and also suggest an effect on T-helper cell type 2 (TH-2) responses.
Publication types
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Clinical Trial
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Comparative Study
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / administration & dosage*
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Adjuvants, Immunologic / adverse effects
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Aluminum Compounds / administration & dosage
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Aluminum Compounds / adverse effects
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Aluminum Compounds / immunology
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Aluminum Compounds / pharmacology
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Antibodies, Bacterial / biosynthesis
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Antigens, Bacterial / administration & dosage
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Antigens, Bacterial / adverse effects
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Antigens, Bacterial / immunology
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Bacterial Proteins / administration & dosage*
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Bacterial Proteins / adverse effects
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Bacterial Proteins / immunology
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Child, Preschool
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Cytokines / biosynthesis
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Female
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Humans
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Immunity, Cellular / drug effects
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Immunity, Cellular / immunology
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Immunoglobulin G / biosynthesis
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Infant
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Lipid A / administration & dosage*
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Lipid A / adverse effects
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Lipid A / analogs & derivatives*
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Lipid A / immunology
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology
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Male
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Phosphates / administration & dosage
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Phosphates / adverse effects
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Phosphates / immunology
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Phosphates / pharmacology
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Polysaccharides, Bacterial / administration & dosage*
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Polysaccharides, Bacterial / adverse effects
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Polysaccharides, Bacterial / immunology
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T-Lymphocyte Subsets / drug effects
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
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Vaccines, Conjugate / administration & dosage
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Vaccines, Conjugate / adverse effects
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Vaccines, Conjugate / immunology
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Vaccines, Synthetic / administration & dosage
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Vaccines, Synthetic / adverse effects
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Vaccines, Synthetic / immunology
Substances
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Adjuvants, Immunologic
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Aluminum Compounds
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Antibodies, Bacterial
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Antigens, Bacterial
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Bacterial Proteins
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Cytokines
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Immunoglobulin G
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Lipid A
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Phosphates
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Polysaccharides, Bacterial
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Vaccines, Conjugate
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Vaccines, Synthetic
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pneumococcal polysaccharide 14 - CRM 197
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aluminum phosphate
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monophosphoryl lipid A