Abstract
Novel adjuvants, such as Toll-like receptors (TLRs) agonists, are needed for the development of new formulations able to circumvent limitations of current vaccines. Among TLRs, TLR7/8 agonists represent promising candidates, as they are well described to enhance antigen-specific antibody responses and skew immunity toward T helper (TH) 1 responses. We find here that the incorporation of the synthetic TLR7/8 ligand 3M-052 in a cationic DOEPC-based liposome formulation shifts immunity toward TH1 responses and elicits strong and long-lasting germinal center and follicular T helper cell responses in adult mice. This reflects the prolonged recruitment of innate cells toward the site of immunization and homing of activated antigen-loaded monocytes and monocyte-derived dendritic cells toward draining lymph nodes. We further show that this adjuvanticity is independent of type I IFN but NF-κB-dependent. Overall, our data identify TLR7/8 agonists incorporated in liposomes as promising and effective adjuvants to enhance TH1 and germinal center responses.
Highlights
Vaccines play a key role against infectious diseases such as smallpox, diphtheria, tetanus, measles and many others
We show that strong and sustained germinal center (GC) B cell and T follicular helper (TFH) cell responses are induced by SPA10, associated with a prolonged recruitment/homing of highly activated antigen-loaded monocytes and monocyte-derived dendritic cells (Mo-DCs) toward the injection site and draining lymph nodes, and that SPA10-mediated B cell adjuvanticity is type I interferon-independent but NF-kB-dependent
We show that cationic liposomes enhance antibody responses through GC B and TFH cell expansion, and that the incorporation of a TLR7/8 ligand markedly prolongs these responses
Summary
Vaccines play a key role against infectious diseases such as smallpox, diphtheria, tetanus, measles and many others. Among the different TLRs, the endosomal TLR7 and TLR8 have been of particular interest since both are expressed by the major human dendritic cell (DC) subsets (plasmacytoid and myeloid DCs, respectively) [5] and TLR7 by human B cells [6, 7]. Both are activated by ssRNA as well as small synthetic molecules such as imidazoquinolines, which can be dual TLR7/8 agonists (e.g. resiquimod (R848)) or TLR7-selective (e.g. imiquimod (R837)) [8]
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