Effect of monophosphoryl lipid A (MPL registered ) on T-helper cells when administered as an adjuvant with pneumocococcal-CRM sub(197) 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 registered ) in 129 healthy toddlers immunized with two doses of nine-valent pneumococcal-CRM sub(197) protein conjugate vaccine (PCV9) combined with 10, 25, or 50 mu g of MPL registered with or without alum (AlPO sub(4)). Vaccine-specific humoral and cell-mediated responses were examined following the second dose of study vaccine. All doses of MPL registered were well-tolerated and a dose-dependent effect of MPL registered on specific cellular responses was observed. The 10 mu g MPL registered dose significantly enhanced CRM sub(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 sub(4). In contrast, CRM sub(197)-specific T-cell proliferation and interferon- gamma production of the 50 mu g MPL registered /AlPO sub(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 mu g MPL registered group and decreased production in the 50 mu g MPL registered /AlPO sub(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 registered -containing and control vaccine groups. These findings demonstrate a dose-dependent effect of MPL registered 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.