The synthetic vaccine that the authors designed was composed of nanoparticles that were similar to a virus in size and structure and contained the TLR4 ligand monophosphoryl lipid A (MPL), the TLR7 ligand R837 (imiquimod) and an antigen. Immunization with this vaccine using haemagglutinin (HA) from H5N1 avian influenza virus as the antigen induced significantly higher antigen-specific antibody responses in mice than a nanoparticle vaccine that contained just one TLR ligand. Similar results were observed when a bacterial antigen was used. The vaccine containing MPL plus R837 also induced the highest titres of virus-specific neutralizing antibodies. So, a combination of TLR ligands in a nanoparticle vaccine is an efficient way to promote humoral immunity. But what is the mechanism of this synergistic TLR-induced response?
Depletion of dendritic cells (DCs) prior to vaccination with the dual TLR ligand nanoparticle vaccine resulted in diminished antibody responses. In addition, reduced antibody titres were observed in immunized mice that specifically lacked B cell expression of important TLR signalling adaptor molecules (MYD88 and TRIF). Together these data indicate that both DCs and B cells are required for the response to this vaccine. Of note, the authors found that TLR4 and TLR7 must be co-expressed by the same B cell in order to induce high levels of antibody following vaccination.
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