Effect of monophosphoryl lipid A (MPL) on T-helper cells when administered as an adjuvant with pneumocococcal-CRM197 conjugate vaccine in healthy toddlers.
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.
Vernacchio
Louis
L
Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. lvernacchio@slone.bu.edu
Bernstein
Henry
H
Pelton
Steve
S
Allen
Carole
C
MacDonald
Kristin
K
Dunn
Jessica
J
Duncan
David D
DD
Tsao
Grace
G
LaPosta
Vincent
V
Eldridge
John
J
Laussucq
Suzanne
S
Ambrosino
Donna M
DM
Molrine
Deborah C
DC
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
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