Programming the magnitude and persistence of antibody responses with innate immunity

Many successful vaccines induce persistent antibody responses that can last a lifetime. The mechanisms by which they do so remain unclear, but emerging evidence indicates that they activate dendritic cells via Toll-like receptors (TLRs). For example, the yellow fever vaccine YF-17D, one of the most successful empiric vaccines ever developed, activates dendritic cells via multiple TLRs to stimulate proinflammatory cytokines. Triggering specific combinations of TLRs in dendritic cells can induce synergistic production of cytokines, which results in enhanced T-cell responses, but its impact on antibody responses remain unknown. Learning the critical parameters of innate immunity that program such antibody responses remains a major challenge in vaccinology. Here we demonstrate that immunization of mice with synthetic nanoparticles containing antigens plus ligands that signal through TLR4 and TLR7 induces synergistic increases in antigen-specific, neutralizing antibodies compared to immunization with nanoparticles containing antigens plus a single TLR ligand. Consistent with this there was enhanced persistence of germinal centres and of plasma-cell responses, which persisted in the lymph nodes for >1.5 years. Surprisingly, there was no enhancement of the early short-lived plasma-cell response relative to that observed with single TLR ligands. Molecular profiling of activated B cells, isolated 7 days after immunization, indicated that there was early programming towards B-cell memory. Antibody responses were dependent on direct triggering of both TLRs on B cells and dendritic cells, as well as on T-cell help. Immunization protected completely against lethal avian and swine influenza virus strains in mice, and induced robust immunity against pandemic H1N1 influenza in rhesus macaques.     

Are household subjective forecasts of personal finances accurate and useful? A directional analysis of the British Household Panel Survey

The purpose of the paper is to analyse the accuracy and usefulness of household subjective forecasts of personal finance. We use non‐parametric directional analysis to assess the subjective forecasts which are based on qualitative judgments. Using the British Household Panel Survey (BHPS) we are able to analyse a large number of individuals over a number of years. We also take into account individual characteristics such as gender, age, education and employment status when assessing their subjective forecasts. The paper extends the existing literature in two ways: the accuracy and usefulness of subjective forecasts, based on directional analysis, are assessed at the household level for the first time. Secondly, we adapt and extend the methods of directional analysis, which are applied to the household panel or longitudinal survey. Copyright © 2008 John Wiley & Sons, Ltd.