Examination of the role of dendritic cells, macrophages and B cells in the function of vaccine adjuvants. (VAC6P.944)

Abstract

Abstract Vaccines are vital in the fight against infectious diseases. Many vaccines are successful because of adjuvants added to their formulations or in the case of live attenuated vaccine because the adjuvant is inherent, however they have been used with little understanding of their mechanisms. PorB, a TLR2 agonist, is the major outer membrane protein of Neisseria meningitidis with potent adjuvant activity. In this study we investigated the role of individual antigen-presenting cell (APC) types in the adjuvant activity of PorB with comparisons to other vaccine adjuvants. WT mice and MyD88 APC floxed mice were immunized three times two weeks apart with ovalbumin (OVA) and either PorB, Alum, MF-59, MPL or CpG. We confirmed MyD88 deletion by qPCR on the purified cells and by measuring cytokines after stimulation with TLR ligand. Analysis of serum indicated that MyD88 in B cells, macrophages and dendritic cells is important for the production of PorB/OVA induced anti-OVA IgG. Alum, a MyD88 independent adjuvant, was able to induce strong anti-OVA IgG in mice that lacked MyD88 in any of these APCs. Interestingly the adjuvant activity of MF-59, which may be MyD88 dependent, were not affected by deletion of MyD88 in the different APC cell types, suggesting that if MyD88 is involved in its adjuvant activity, it must be due to stimulation of other cell types. These insights will aid in vaccine development by allowing more intelligent and judicious use of these and other vaccine adjuvants.