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Programming the magnitude and persistence of antibody responses with innate immunity
Vaccines given a boost A feature of many successful vaccines is the induction of memory B cells and long-lived plasma cells that can secrete neutralizing antibodies for a lifetime. The mechanisms that stimulate such persistent responses remain poorly understood. Bali Pulendran and colleagues show th...
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Published in: | Nature (London) 2011-02, Vol.470 (7335), p.543-547 |
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Main Authors: | , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Vaccines given a boost
A feature of many successful vaccines is the induction of memory B cells and long-lived plasma cells that can secrete neutralizing antibodies for a lifetime. The mechanisms that stimulate such persistent responses remain poorly understood. Bali Pulendran and colleagues show that nanoparticles containing two Toll-like receptor ligands, proteins with important roles in innate immunity, can boost the magnitude and persistence of vaccine-elicited antibody responses in primates, improving vaccine-mediated protection against influenza virus.
Here it is shown that nanoparticles containing two Toll-like receptor ligands can boost the magnitude and persistence of vaccine-elicited antibody responses in primates, improving vaccine-mediated protection against influenza virus.
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)
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,
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. For example, the yellow fever vaccine YF-17D, one of the most successful empiric vaccines ever developed
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, activates dendritic cells via multiple TLRs to stimulate proinflammatory cytokines
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,
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. Triggering specific combinations of TLRs in dendritic cells can induce synergistic production of cytokines
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, 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 av |
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ISSN: | 0028-0836 1476-4687 |
DOI: | 10.1038/nature09737 |