Effect of monophosphoryl lipid A (MPL (R)) on T-helper cells when administered as an adjuvant with pneumocococcal-CRM197 conjugate vaccine in healthy toddlers

摘要

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(R)) in 129 healthy toddlers immunized with two doses of nine-valent pneumococcal-CRM197 protein conjugate vaccine (PCV9) combined with 10, 25, or 50 mug of MPL(R) with or without alum (AlPO4). Vaccine-specific humoral and cell-mediated responses were examined following the second dose of study vaccine. All doses of MPL(R) were well-tolerated and a dose-dependent effect of MPL(R) on specific cellular responses was observed. The 10 mug MPL(R) dose significantly enhanced CRM197-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 AlPO4. In contrast, CRM197-specific T-cell proliferation and interferon-gamma production of the 50 mug MPL(R)/AlPO4 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 mug MPL(R) group and decreased production in the 50 mug MP(R)/AlPO4 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(R)-containing and control vaccine groups. These findings demonstrate a dose-dependent effect of MPL(R) 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.