title: Effect of monophosphoryl lipid A (MPL) on T-helper cells when administered as an adjuvant with pneumocococcal-CRM197 conjugate vaccine in healthy toddlers.
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.
authors.affiliation: Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. lvernacchio@slone.bu.edu
authors.forename: Louis
authors.initials: L
authors.lastname: Vernacchio
authors.forename: Henry
authors.initials: H
authors.lastname: Bernstein
authors.forename: Steve
authors.initials: S
authors.lastname: Pelton
authors.forename: Carole
authors.initials: C
authors.lastname: Allen
authors.forename: Kristin
authors.initials: K
authors.lastname: MacDonald
authors.forename: Jessica
authors.initials: J
authors.lastname: Dunn
authors.forename: David D
authors.initials: DD
authors.lastname: Duncan
authors.forename: Grace
authors.initials: G
authors.lastname: Tsao
authors.forename: Vincent
authors.initials: V
authors.lastname: LaPosta
authors.forename: John
authors.initials: J
authors.lastname: Eldridge
authors.forename: Suzanne
authors.initials: S
authors.lastname: Laussucq
authors.forename: Donna M
authors.initials: DM
authors.lastname: Ambrosino
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Molrine
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D017607:Aluminum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007223:Infant; D008050:Lipid A / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D010710:Phosphates / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D007074:Immunoglobulin G; D008050:Lipid A; D010710:Phosphates; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate; D014614:Vaccines, Synthetic; C092298:pneumococcal polysaccharide 14 - CRM 197; C012714:aluminum phosphate; C048436:monophosphoryl lipid A